11 October 2007
Designer Drosophilla... Who wants one?
With the discovery of the ability to manipulate novel phenotypes by the the Heat Shock Protein 90 (HSP90), it has presented the possibility for a person to choose what something looks like. So far it is only in Drosophilla and a plant, but if there is the slightest chance that this knowledge could be passed over, then the possibilities are endless. People could change their natural hair colour, skin colour, maybe even metabolism, and combat obesity. But at the moment it is limited to fruit flies and plants. But hey, some people can dream.
10 October 2007
Bacteria at war with Antibiotics
EVOLUTION SOS
Antibiotic resistance may not simply be the random chance of a mutation occurring and selectively favoured by the environment, but induced by certain bacteria to occur in the hope for a better solution. A recent study has found that antibiotic resistance to ciprofloxacin and rifampicin involves a DNA binding protein LexA. In the presence of LexA bacteria are able to rapidly undergo an increased mutation rate and consequently develop antibiotic resistance though favorably selected mutations. When LexA is absent no resistance can occur. This indicates that when these mutation inducing proteins are inactive resistance is unable to develop and evolution can therefore be halted, disagreeing with previous statements that evolution is inevitable!
Student Number 41167661
Reference
Romesberg, F. E, R. T. Cirz, J. K. Chin, D. R. Andes, V. Crécy-Lagard, and W. A. Craig, 2007. Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biol 3(6): e176.
Antibiotic resistance may not simply be the random chance of a mutation occurring and selectively favoured by the environment, but induced by certain bacteria to occur in the hope for a better solution. A recent study has found that antibiotic resistance to ciprofloxacin and rifampicin involves a DNA binding protein LexA. In the presence of LexA bacteria are able to rapidly undergo an increased mutation rate and consequently develop antibiotic resistance though favorably selected mutations. When LexA is absent no resistance can occur. This indicates that when these mutation inducing proteins are inactive resistance is unable to develop and evolution can therefore be halted, disagreeing with previous statements that evolution is inevitable!
Student Number 41167661
Reference
Romesberg, F. E, R. T. Cirz, J. K. Chin, D. R. Andes, V. Crécy-Lagard, and W. A. Craig, 2007. Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biol 3(6): e176.
Bacteria Resilience = Evolution at its Best
Evolution Under Intrinsic Control
Bacteria and their resistance to antibiotics have long been used as examples of Darwin’s theory of evolution. The bacteria resistance against antibiotics was seen as an example of natural selection where any random mutant that was produced that was immune would soon become selected, thus passing on its genetic traits to offspring.
This experiment showed that the bacteria did not produce random mutants to combat the antibiotics. Floyd Romesberg and fellow researchers found that the bacteria actively increase the number of mutants produced in order to increase the chance of survival. This is not all they found though, they also found that bacteria will try and fix themselves before they take the drastic steps to mutate.
Floyd Romesberg’s experiment linked the production of mutants to the protein Lex-A, this protein accelerates the production of mutant bacteria however when the bacteria are faced with a strong antibiotic the bacteria produces Lex-A allowing for an increased number of mutants to be produced.
These findings have given new light to antibiotic resistance and allow for vast implications in the medical field. Bacteria with the protein Lex-A suppressed were found to acquire no resistance to antibiotics where as the same bacteria with Lex-A acquired immunity to the same antibiotic.
In conclusion these finding do not show that Darwin was wrong, it just shows that the process of evolution is programmed into us and life can take control over the once thought of random processes.
Bacteria and their resistance to antibiotics have long been used as examples of Darwin’s theory of evolution. The bacteria resistance against antibiotics was seen as an example of natural selection where any random mutant that was produced that was immune would soon become selected, thus passing on its genetic traits to offspring.
This experiment showed that the bacteria did not produce random mutants to combat the antibiotics. Floyd Romesberg and fellow researchers found that the bacteria actively increase the number of mutants produced in order to increase the chance of survival. This is not all they found though, they also found that bacteria will try and fix themselves before they take the drastic steps to mutate.
Floyd Romesberg’s experiment linked the production of mutants to the protein Lex-A, this protein accelerates the production of mutant bacteria however when the bacteria are faced with a strong antibiotic the bacteria produces Lex-A allowing for an increased number of mutants to be produced.
These findings have given new light to antibiotic resistance and allow for vast implications in the medical field. Bacteria with the protein Lex-A suppressed were found to acquire no resistance to antibiotics where as the same bacteria with Lex-A acquired immunity to the same antibiotic.
In conclusion these finding do not show that Darwin was wrong, it just shows that the process of evolution is programmed into us and life can take control over the once thought of random processes.
Student # 40798460
Reference
Romesberg, F. E, R. T. Cirz, J. K. Chin, D. R. Andes, V. Crécy-Lagard, and W. A. Craig, 2007. Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biol 3(6): e176.
Taking a New Direction with Evolution!
How do bacteria become resistant to antibiotics? They evolve! They evolve quickly too, in a study conducted by Watson et al, mutant strains of Escherichia coli (E. coli) with resistance to the antibiotic trimethoprim (TMP) were obtained after only three generations. How is this possible? Well, taking into account the popular theory of directed evolution, results from this study show that not only can E. coli mutate to overcome the effects of TMP, but the bacterium has the ability to simultaneously increase enzymatic activity, which also reduces the effect of TMP.
Directed evolution was used in this study as a protocol to simulate natural evolutionary processes. Dihydrofolate reductase (DHFR), the target of the antifolate TMP, developed reduced binding affinity for the drug as a result of several mutations. Thus DHFR, with its huge evolutionary potential, does not make it a suitable drug target. It was concluded therefore that locating enzymes which are “at or near their evolutionary limit” (Watson et al, 2007) will be a viable direction for the future design of effective antibacterial drugs. So the bacterial mutations of today, whilst dodging the effects of current antibiotics, will eventually be tackled by drugs specifically aimed at the mega-evolved enzymes of tomorrow!
References:
Watson M, Liu J and Ollis, D, 2007, Directed evolution of trimethoprim resistance in Escherichia coli, FEBS Journal, vol 274, pp 2661-2671.
Directed evolution was used in this study as a protocol to simulate natural evolutionary processes. Dihydrofolate reductase (DHFR), the target of the antifolate TMP, developed reduced binding affinity for the drug as a result of several mutations. Thus DHFR, with its huge evolutionary potential, does not make it a suitable drug target. It was concluded therefore that locating enzymes which are “at or near their evolutionary limit” (Watson et al, 2007) will be a viable direction for the future design of effective antibacterial drugs. So the bacterial mutations of today, whilst dodging the effects of current antibiotics, will eventually be tackled by drugs specifically aimed at the mega-evolved enzymes of tomorrow!
References:
Watson M, Liu J and Ollis, D, 2007, Directed evolution of trimethoprim resistance in Escherichia coli, FEBS Journal, vol 274, pp 2661-2671.
Mice can be EMO too!
Depression and anxiety are a major problem in today’s modern human society. Although these troubles can be triggered by environmental factors, an individual’s genetics can play a large role in their susceptibility to these illnesses. To better understand the causes of depression and anxiety, it is important to map the genes underlying quantitative trait loci know to play a role in complex phenotypes such as emotionality (EMO). Despite recent breakthroughs in examining and mapping the quantitative trait loci that control these complex traits, the process is far from perfect. It is these genetic factors that have recently become of great interest to geneticists, in the hope of understanding how humans cope with depression and anxiety.
However, in order to understand human emotionality, scientists must first understand emotionality in smaller animals that are more convenient to experiment on, mice, for example. Many traits in mice and humans, including emotionality, exhibit high levels of quantitative trait loci concordance and by examining the quantitative trait loci that control emotionality in mice, it may be possible to identify the genes in human beings that contribute to emotionality.
Written by s4122887
References
Mackay, Trudy. (2004) Complementing complexity, Nature Genetics, Vol 36, Number 11, 1145-7
Willis-Owen, S.A.G. & Flint, J. (2007), Identifying the genetic determinants of emotionality in humans: insights from rodents. Neuroscience and Behavioural Reviews, 31, 115-124.
However, in order to understand human emotionality, scientists must first understand emotionality in smaller animals that are more convenient to experiment on, mice, for example. Many traits in mice and humans, including emotionality, exhibit high levels of quantitative trait loci concordance and by examining the quantitative trait loci that control emotionality in mice, it may be possible to identify the genes in human beings that contribute to emotionality.
Written by s4122887
References
Mackay, Trudy. (2004) Complementing complexity, Nature Genetics, Vol 36, Number 11, 1145-7
Willis-Owen, S.A.G. & Flint, J. (2007), Identifying the genetic determinants of emotionality in humans: insights from rodents. Neuroscience and Behavioural Reviews, 31, 115-124.
RNA Silencing: A Newly Discovered Mechanism for Control of Flowering Time
Current research by Herr et al (2006) has shown RNA silencing pathways may be induced via defective RNA transcription, consequently affecting the flowering time in Arabidopsis.
The study was conducted using enhanced silencing phenotype (esp) mutant Arabidopsis plants and it has been identified that proteins involved in RNA transcript processing and 3’ end formation can activate RNA silencing pathways. Two such proteins, symplekin/PTA1 homologue and CPSF100 in Arabidopsis form part a complex with FY, a protein important in the regulation of FCA processing. Where FY is defective, misprocessing of FCA can occur. Consequently, the autoregulated alternate splicing mechanism in 3’ end formation is affected and increased silencing of the FCA-β mRNA transcript occurs. Interestingly, early flowering in the esp mutant is also observed.
In the esp mutants, FCA-β mRNA is silenced in a RDR6-dependent manner and thus Herr et al (2006) reached the conclusion that small interfering (siRNA) are produced from aberrant FCA-β RNA and is the causative agent initiating RNA silencing. It was also suggested that the siRNAs produced from aberrant FCA-β RNA may also silence the flowering suppressor genes, which provides an explanation for the early flowering observed in mutant phenotypes.
The overall findings of research have correlated increased RNA silencing as a result of defective transcript processing, which subsequently influences flowering time control in Arabidopsis.
Sarah Woolner, 41014420
Reference:
Herr AJ, Molnàr A, Jones A, Baulcombe DC (2006). Defective RNA processing enhances RNA silencing and influences flowering of Arabidopsis. Proc Natl Acad Sci U S A. 103(41):14994-5001.
The study was conducted using enhanced silencing phenotype (esp) mutant Arabidopsis plants and it has been identified that proteins involved in RNA transcript processing and 3’ end formation can activate RNA silencing pathways. Two such proteins, symplekin/PTA1 homologue and CPSF100 in Arabidopsis form part a complex with FY, a protein important in the regulation of FCA processing. Where FY is defective, misprocessing of FCA can occur. Consequently, the autoregulated alternate splicing mechanism in 3’ end formation is affected and increased silencing of the FCA-β mRNA transcript occurs. Interestingly, early flowering in the esp mutant is also observed.
In the esp mutants, FCA-β mRNA is silenced in a RDR6-dependent manner and thus Herr et al (2006) reached the conclusion that small interfering (siRNA) are produced from aberrant FCA-β RNA and is the causative agent initiating RNA silencing. It was also suggested that the siRNAs produced from aberrant FCA-β RNA may also silence the flowering suppressor genes, which provides an explanation for the early flowering observed in mutant phenotypes.
The overall findings of research have correlated increased RNA silencing as a result of defective transcript processing, which subsequently influences flowering time control in Arabidopsis.
Sarah Woolner, 41014420
Reference:
Herr AJ, Molnàr A, Jones A, Baulcombe DC (2006). Defective RNA processing enhances RNA silencing and influences flowering of Arabidopsis. Proc Natl Acad Sci U S A. 103(41):14994-5001.
Stress: transposon turn-on
Stress: transposon turn-on
Transposons are DNA sequences capable of "jumping" from one genomic location to another. One type of transposon uses the enzyme tramsposase to move about the genome, while another known as a ‘retrotransposon’ encodes two enzymes, reverse transcriptase, which transcribes the mRNA of the transposon into DNA, and integrase, which then integrates the transposon into the genome. Ty5 is one such retrotransposon of S. cerevisiae, and for a while it has been observed that Ty5 inserts preferentially into a non-transcribed region of the genome near the telomeres.
This year the mechanism behind this specific integration was discovered: it was found that, under normal conditions, one amino acid located in the ‘targeting domain’ of integrase becomes phosphorylated, and it is this phosphorylation that is required for the transposon to be inserted into the heterochromatin where it will not damage the gene-coding sequences.
But what is really interesting is that under conditions of stress, it was observed that the integrase was not phosphorylated, and consequently, the transposons were not inserted into the telomere sequences but rather, into transcribed DNA, where they caused mutations.
It seems then, that the preference for integration is controlled by the cell and not the transposon. But why would a cell want to mutate gene-coding sequences? The fact that stress caused changes in the specificity of integration of transposons effectively demonstrates the increasingly accepted notion that the induced mutation increases genetic variation upon which selection may operate, thereby increasing the chances of adaptation.
by Alicia Grealy
Student number: 41196504
References
Primary:
Ebina H & Levin HL, 2007, ‘Stress management: how cells take control of their transposons’, Molecular Cell, vol.27, pp.180-181.
Transposons are DNA sequences capable of "jumping" from one genomic location to another. One type of transposon uses the enzyme tramsposase to move about the genome, while another known as a ‘retrotransposon’ encodes two enzymes, reverse transcriptase, which transcribes the mRNA of the transposon into DNA, and integrase, which then integrates the transposon into the genome. Ty5 is one such retrotransposon of S. cerevisiae, and for a while it has been observed that Ty5 inserts preferentially into a non-transcribed region of the genome near the telomeres.
This year the mechanism behind this specific integration was discovered: it was found that, under normal conditions, one amino acid located in the ‘targeting domain’ of integrase becomes phosphorylated, and it is this phosphorylation that is required for the transposon to be inserted into the heterochromatin where it will not damage the gene-coding sequences.
But what is really interesting is that under conditions of stress, it was observed that the integrase was not phosphorylated, and consequently, the transposons were not inserted into the telomere sequences but rather, into transcribed DNA, where they caused mutations.
It seems then, that the preference for integration is controlled by the cell and not the transposon. But why would a cell want to mutate gene-coding sequences? The fact that stress caused changes in the specificity of integration of transposons effectively demonstrates the increasingly accepted notion that the induced mutation increases genetic variation upon which selection may operate, thereby increasing the chances of adaptation.
by Alicia Grealy
Student number: 41196504
References
Primary:
Ebina H & Levin HL, 2007, ‘Stress management: how cells take control of their transposons’, Molecular Cell, vol.27, pp.180-181.
Complex Traits In Mice
Among the many complex traits that are available in mice, there are a couple of attributes which are proven to be handy in many genetics researches. One of the main complex psychological traits is in the studying of molecular and genetical cells, such as diseases. This is due to the fact that with these studies on the mice cells, which are quite similar to the human cell, geneticist and researchers are able to develop vaccine and many others in a shorter period of time. According to Geoff Spencer and based on researches carried out, mice are a much suitable organism in probing for immunization, nervous, and the cardiovascular systems which are shared among most mammals, including the Homo sapiens (human being). According to researchers in the Genetics Society of America, all of those are true in some ways, but the magnitude of the interaction has not been measured very often. And according to researches carried out from a study of a number of around 2500 mice which are heterozygous in their genetic information, there are 88 complex traits inherited, which includes a few models of common diseases in human, that are like asthma, anxiety, diabetes type 2 and many more. Therefore, the complex traits in mice can lead to many essential researches to be much successful.
Jern Hei NG (Michael)<41350191>
The End of Bacterial Antibiotic Resistance?
In modern society antibiotic treatments have been far too heavily relied upon and consequently there has been a staggering increase in antibiotic resistance of many strains of bacteria. Bacterial infections are becoming harder and harder to treat as the range of antibiotics available for treatment are failing. Through a better understanding of the process of this adaptation, a new approach to treating these microorganisms is in the future. The function of LexA, a DNA binding protein is known to influence the development of resistance of bacteria to antibiotics through the many mutations that occur during the SOS response. These mutations can sometimes lead to antibiotic resistance. Studies of LexA mutants have shown that bacterial infections are unable to evolve and adapt when exposed to DNA damage, through its inability to mutate. Scientists hope that small molecules can be introduced to antibiotics to specifically target the LexA protein. This would render it incapable of influencing the evolution of the bacteria. This would stop the bacterial infection and once again allow the human population to rely on one of the greatest modern scientific discoveries.
References
Johnston, N, (2005), ‘Reversing the evolution of antibiotic resistance’, Drug Discovery Today, Vol. 10, Iss. 19, pp. 1267
Stix, G, (2006), 'An Antibiotic Resistance Fighter’, Scientific American, Vol. 294, Iss. 4, pp. 80-83
Stix, G, (2006), 'An Antibiotic Resistance Fighter’, Scientific American, Vol. 294, Iss. 4, pp. 80-83
Student number: 41187333
Hsp90 the Eukaryotic Chaperone: allowing plants to kill themselves, but only a little.
In ‘Molecular mechanisms of canalization: Hsp90 and beyond’ the authors explain that Hsp90 acts as a chaperone, ensuring proper folding of client proteins involved in cellular function and phenotype. In the absence of Hsp90 the client proteins become unstable and are rapidly degraded. Hsp90 provides protection against environmental stresses and allows the production of a stable phenotype (canalisation). This important function is why Hsp90 has been discovered in all eukaryotes studied so far.
So are the proteins it protects actually important?
Studies have shown that in plants Hsp90 has a close association with R-proteins which produce localised cell death when activated by pathogen-specific effecter molecules. This as well as involvement in light perception, seedling etiolation, and gravitropism make Hsp90 an important chaperone in plants.
So Hsp90 is certainly important in the heat shock response of organisms, but it appears that it has a range of important functions, in a wide variety of organisms.
Queitsch, C. S. (2002). Nature , 618-624.
QUEITSCH, N. S. (2007). Molecular mechanisms of canalization: Hsp90 and beyond. Journl of Bioscience , 457-463.
Rutherford, S. L. (1998). Nature , 336-342.
So Hsp90 is certainly important in the heat shock response of organisms, but it appears that it has a range of important functions, in a wide variety of organisms.
Queitsch, C. S. (2002). Nature , 618-624.
QUEITSCH, N. S. (2007). Molecular mechanisms of canalization: Hsp90 and beyond. Journl of Bioscience , 457-463.
Rutherford, S. L. (1998). Nature , 336-342.
Complex traits and the Semaphorin 5c gene in Drosophila
Certain behaviors are considered complex traits that are influenced by the expression of multiple pleiotropic genes. Looking at Drosophilia melanogaster, we are able to look at the effects of the hypomorphic disruption of the early developmental gene Semaphorin-5c. During the Benzaldehyde avoidance assay, flies were put into a vial and the odor was introduced on a cotton swab. The number of flies that were present in the vial further away from the odor were recorder every five seconds for one minute. This was only the first method. The following methods included a quantitative complementation test, phenotypic reversion through P-element excision, Transgenic rescue, whole-mount immunohistochemistry, the antibody that was obtained, microscopy, morphometric analysis, transcriptional profiles, and Epistasis. The results were as followed. A P-element insertion near the Sema-5c gene concluded in aberrant olfactory behavior. P[GT1]-element disruption of Sema-5c resulted in the presence of the smell-impaired phenotype. Neuroanatomical consequences of disruption of the Sema-5c gene. Sema-5c gene also altered genome wide expression levels. All of these results conclude that the hypomorphic mutation of an early development gene has a consequence of genome wide transcriptional problems and alterations in the brain structure which results in the impairment of adult behavior.
Heather Davis
41347173
Reference
Rollmann, Stephanie M., Yamamoto, Akihiko. 2007. The Early Developmental Gene Semaphorin 5c Contributes to Olfactory Behavior in Adult Drosophila. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1894621
Heather Davis
41347173
Reference
Rollmann, Stephanie M., Yamamoto, Akihiko. 2007. The Early Developmental Gene Semaphorin 5c Contributes to Olfactory Behavior in Adult Drosophila. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1894621
Emotions in Mice!
Emotion is a complex psychological trait. Its function is to moderate an organisms response to stress. The mouse contains several number of attributes which have proven useful to genetic research. These comprise of short gestation period, an early puberty, a short oestrus cycle and their propensity to produce large litters. These factors, along with directed mating and firm environmental control make the mouse an invaluable tool for complex trait classification. There are a variety of behavioural phenotypes that are currently used as informative procedures of the organism’s emotionality profile. The most widely used experiment is the open-field apparatus; a circular white, brightly lit and fully enclosed arena, within which behaviour can be tenuously monitored. Negative correlation is exhibited by defecation and ambulation, based on observations that intense fear can result such behaviour. A recent behavioural analysis of more nearly 1700 mice showed that five genetically separable composite measures of anxiety were identified. Quantitative trait loci (OTL) were found to contribute towards variance of the measures.
By Pratyusha Krishna Mirajkar
41164455
References
1) Mackay, T.F.C.(2004) Complementing Complexity, Nature Genetics, 36(11) 1145-1147
2) Willis-Owen S.A.G, Flint J. (2006) The genetic basis of emotional behaviour in mice, European Journal of Human Genetics, 14, 721–728
By Pratyusha Krishna Mirajkar
41164455
References
1) Mackay, T.F.C.(2004) Complementing Complexity, Nature Genetics, 36(11) 1145-1147
2) Willis-Owen S.A.G, Flint J. (2006) The genetic basis of emotional behaviour in mice, European Journal of Human Genetics, 14, 721–728
From Nervous Mice to Neurotic Humans
While the study of anxiety in mice using QTLs is both ground-breaking and remarkable, the reality is that the ultimate goal is to understand the genetic basis of such traits in humans. Similar techniques have been used to narrow down the QTLs and have led to some very interesting discoveries.
Five loci have been identified that affect anxiety related traits, however some of these acted only in males or females. This indicates that gender must be taken into account when considering such traits.
Some of the loci discovered in humans seem to relate specifically to fairly narrowly defined disorders such as panic disorders and phobias. Other sites however were linked to panic disorder and neuroticism but not to agoraphobia or simple phobias, traits which would appear to be related.
One of the five loci in mouse that was linked to anxiety was mapped to a region homologous to the loci 14p in humans which has been linked predominately to phobias. This suggests that the information from mouse QTL studies could be used to discover loci in humans and further our knowledge of disorders such as anxiety and phobias.
Eleanor McDonald
40855130
References
Mackay, Trudy. (2004) Complementing complexity, Nature Genetics, Vol 36, Number 11, 1145-7
Villafuerte, S and Burmeister, (2003) M. Untangling genetic networks of panic, phobia, fear and anxiety. Genome Biology, Vol 4, Issue 8, Article 224
Five loci have been identified that affect anxiety related traits, however some of these acted only in males or females. This indicates that gender must be taken into account when considering such traits.
Some of the loci discovered in humans seem to relate specifically to fairly narrowly defined disorders such as panic disorders and phobias. Other sites however were linked to panic disorder and neuroticism but not to agoraphobia or simple phobias, traits which would appear to be related.
One of the five loci in mouse that was linked to anxiety was mapped to a region homologous to the loci 14p in humans which has been linked predominately to phobias. This suggests that the information from mouse QTL studies could be used to discover loci in humans and further our knowledge of disorders such as anxiety and phobias.
Eleanor McDonald
40855130
References
Mackay, Trudy. (2004) Complementing complexity, Nature Genetics, Vol 36, Number 11, 1145-7
Villafuerte, S and Burmeister, (2003) M. Untangling genetic networks of panic, phobia, fear and anxiety. Genome Biology, Vol 4, Issue 8, Article 224
ATTENTION; Doctors, Nurses, Allied Health Professionals and Students.
Antibiotic resistant bacteria are emerging in today’s society as a major health and economic problem. Through the misuse and overuse of antibiotics we are seeing a major increase in both gram-positive and gram-negative multiple resistant bacteria. If we do not curve the use of antibiotics and have an increased focused approach across the broad spectrum we will see an increase to the cost of patient treatment and patient mortality (Marin H et al 2001).
It has been found that through a study by Floyd Romesberg that bacteria can develop resistance without contact with other bacteria. The study using ciproflaxin and rifampicin it was discovered bacteria are able to develop antibiotic resistance by preventing repression of the SOS response; therefore mutation is able to occur (Gene M 2005).
A mechanism involving both RecA and LexA has been found to be integral to the development of antibiotic resistance. LexA aids in the mechanism of resistance by repressing the SOS response to damage by binding to RecA which forms around the DNA, splitting it and releasing the depression. If bacteria are able to develop resistance on their own are we going to be able to stop the increase of infection (Gene M 2005)?
In order to decrease the number patients infected with antibiotic resistant bacteria a more nationalised approach needs to be looked at. Protocols and guidelines need to be addressed to prevent unnecessary use and increase the effectiveness of antibiotics (Marin H et al 2001).
It has been found that through a study by Floyd Romesberg that bacteria can develop resistance without contact with other bacteria. The study using ciproflaxin and rifampicin it was discovered bacteria are able to develop antibiotic resistance by preventing repression of the SOS response; therefore mutation is able to occur (Gene M 2005).
A mechanism involving both RecA and LexA has been found to be integral to the development of antibiotic resistance. LexA aids in the mechanism of resistance by repressing the SOS response to damage by binding to RecA which forms around the DNA, splitting it and releasing the depression. If bacteria are able to develop resistance on their own are we going to be able to stop the increase of infection (Gene M 2005)?
In order to decrease the number patients infected with antibiotic resistant bacteria a more nationalised approach needs to be looked at. Protocols and guidelines need to be addressed to prevent unnecessary use and increase the effectiveness of antibiotics (Marin H et al 2001).
Written by: Simon L Troth (s4139593)
1. Marin H. Kollef, MD, and Victoria J. Fraser, MD. (2001). Antibiotic Resistance in the Intensive Care Unit. Annals of Internal Medicine, Volume 134 Issue 4, pages 298-314.
2. Gene M (2005). Evolution under intrinsic control.http://www.idthink.net/biot/lexA/index.html
3. Dent S (2000). Deadly risks of antibiotic overuse warrant widespread education. FP Report March 2000 • Volume 6 • Number 3
In Soviet Russia, Heat-shock proteins regulate you!
In recent years, extensive research has been conducted into the functions of specific chaperones known as Heat-shock Proteins (Hsp), and the responses they mediate. Heat-shock proteins are a form of cellular defense employed by an organism when faced with harsh environmental conditions and deleterious genetic mutation. Massimo Pigliucci revealed the effects of inhibiting or altering the expression of a particular Heat-shock protein (Hsp90) gene within two small organisms; the fruit fly and Arabidopsis thaliana plant. The results revealed hidden genetic mutations that had previously been buffered by the chaperone, proving that heat-shock proteins play an important role in maintaining a balance between stability and change. What about other stresses such as physiological changes? Does Hsp90 provide some means of protection against normal abnormalities induced by the organism’s own body? A study conducted by Gordon P. Meares and colleagues, tested this theory by measuring the effect of Hsp90 inhibition on the activation of Akt, an important signaling molecule needed for glucose transport. After inhibiting Hsp90 with geldanamycin, amplified Akt phosphorylation, induced by insulin, was observed. Upon removal of the inhibitor, Hsp90 began to regulate Akt signaling by facilitating phosphatase-mediated dephosphorylation of Akt. These observations indicate that Hsp90 normally plays an important role in buffering these signals.
Thus, Hsp90 not only buffers the cellular effects brought upon by mutations and environmental stresses, but also buffers physiological activities of the body necessary for survival.
Daniel Tang
41291726
Primary Source
Gordon P. Meares, Anna A. Zmijewska and Richard S. Jope, (2004), Heat shock protein-90 dampens and directs signaling stimulated by insulin-like growth factor-1 and insulin, FEBS Letters, Vol. 574 Issues 1-3, pp 181-186
Secondary Source
Pigliucci, M. (2002). Developmental genetics: Buffer zone. Nature, Vol. 417, pp 598-599
The Genetic Variation of Obesity
Will fruit flies ‘shape’ not only our bodies but also our future? Exploration of how Drosphila melangaster fruit flies are models used for examining obesity variation involved in mammals. Maria De Luca et al, carried out studies on D. Melangaster fruit flies, to discover the genes involved in the mammalian adipocyte differentiation and fat storage, by examining the quantitative trait loci (QTLs) of Triacylglcerol (TAG) storage. Using both QTL genetic mapping techniques on 68 recombinant inbred lines, interval mapping and Bayesian epistatic methods, the mapping location of QTLs affecting TAG storage where found. In addition, quantitative deficiency mapping were carried out to identify the candidate genes affecting the obesity trait within one of the QTLs identified to the second chromosome. The quantitative complementation tests were then used to finely map the QTLs found.
As a result, the variations of TAG storage in fruit flies were controlled by different genetic mechanisms and different sets of QTLs in male and female flies. A total of 7-8 QTLs were found to effect TAG storage. Two QTLs affecting TAG storage in both sexes and two QTLs were male-specific epistatic interaction. Also, closely linked QTLs on chromosome 2 were found to have a female-specific variation in TAG storage.
By Natasha Ferber
41237706
Reference:
De Luca, M., Yi, N., Allison, D.B., Leips, J and Ruden, D.M. (2005) “Mapping Quantitative Trait Loci Affecting Variation in Drosophila Triacylglycerol Storage”, Obesity Research, 13: 1596-1605
SOS-Mediated Evolution
It was previously thought that evolution was a random process due to DNA mutations that just randomly happen. Recent research suggests otherwise, it is now thought that the evolution of resistance to antibiotics in some microbes isn’t as ‘random’ as previously thought.
Many microbes react to environmental stress, such as an antibiotic like ciprofloxacin, by undergoing the SOS response. Ciprofloxacin causes double stranded breaks in DNA and affect the DNA gyrase. It is now thought that many microbes, including S. aureus, intentionally undergo SOS to create greater genetic variation in the affected site in hope that resistance will ‘evolve’.
But what makes S. aureus unique? And could possibly make it develop resistance to so many antibiotics so easily? This article suggests that the SOS response is not the only phenomena that the cell undergoes when under stress. Can antibiotic resistance to an antibiotic such as ciprofloxacin go as far as to affect the metabolism of the bacteria too?
Could a change in a metabolic pathway such as the TCA cycle have such a large effect on the virulence, persistence and resistance of the bacteria? The article by Ryan T Cirz et. al. suggests that this is a major factor in this bacteria’s ability to develop antibiotic resistance so easily.
http://portal.isiknowledge.com.ezproxy.library.uq.edu.au/portal.cgi/wos/?Init=Yes&SID=4C8E3O2HHghmAGok4fA
Reference
Cirz RT (Cirz, Ryan T.), Jones MB (Jones, Marcus B.), Gingles NA (Gingles, Neill A.), Minogue TD (Minogue, Timothy D.), Jarrahi B (Jarrahi, Behnam), Peterson SN (Peterson, Scott N.), Romesberg FE (Romesberg, Floyd E.), 2007 ‘Complete and SOS-Mediated Response of S. aureus to the Antibiotic Ciprofloxacin’ Journal of Bacteriolog Vol 189 (2) pages531-539 J
by Daniel Kluver (41184239)
Many microbes react to environmental stress, such as an antibiotic like ciprofloxacin, by undergoing the SOS response. Ciprofloxacin causes double stranded breaks in DNA and affect the DNA gyrase. It is now thought that many microbes, including S. aureus, intentionally undergo SOS to create greater genetic variation in the affected site in hope that resistance will ‘evolve’.
But what makes S. aureus unique? And could possibly make it develop resistance to so many antibiotics so easily? This article suggests that the SOS response is not the only phenomena that the cell undergoes when under stress. Can antibiotic resistance to an antibiotic such as ciprofloxacin go as far as to affect the metabolism of the bacteria too?
Could a change in a metabolic pathway such as the TCA cycle have such a large effect on the virulence, persistence and resistance of the bacteria? The article by Ryan T Cirz et. al. suggests that this is a major factor in this bacteria’s ability to develop antibiotic resistance so easily.
http://portal.isiknowledge.com.ezproxy.library.uq.edu.au/portal.cgi/wos/?Init=Yes&SID=4C8E3O2HHghmAGok4fA
Reference
Cirz RT (Cirz, Ryan T.), Jones MB (Jones, Marcus B.), Gingles NA (Gingles, Neill A.), Minogue TD (Minogue, Timothy D.), Jarrahi B (Jarrahi, Behnam), Peterson SN (Peterson, Scott N.), Romesberg FE (Romesberg, Floyd E.), 2007 ‘Complete and SOS-Mediated Response of S. aureus to the Antibiotic Ciprofloxacin’ Journal of Bacteriolog Vol 189 (2) pages531-539 J
by Daniel Kluver (41184239)
Doctors Look Out: A life without antibiotic resistance is in the near future!!
Doctors Look Out: A life without antibiotic resistance is in the near future!!
By: Alyssa Firkus
41331444
Antibiotic resistance has been a tremendous hurdle for battling many fatal diseases, such as cancer. Understanding the evolution of antibiotic resistance could further future drug design. Recent studies have shown that random mutations may not be random at all. Bacteria ensure that these mutations happen, "purposeful mutations. These "purposeful mutations" are essential in making sure there is plenty of variability, this is esseantial to form antibiotic resistance. Floyd Romesberg and colleagues tested two antibiotics, ciprofloxacin and rifampicin, to discover that Lex A cleavage is needed for the evolution of resistive, in both antibiotics tested, it causes bacteria not to develop resistance (Gene, 2005). Lex A stops the SOS response, which reacts in the cell when DNA synthesis is inhibited (Gene 2005). The removal of Lex A keeps the cell from being able to adapt. What can this mean for life? What genes can be controlled?
These findings look promising for future drug design, small molecules when administered with antibiotics could prevent bacteria from attaining resistance mutations. (Johnston 2005). Could this fight against antibiotic resistance lead to the reverse of other common resistances? Could this change previous existing resistances?
PrimaryReferences
Gene, M. (2005). “Evolution Under Intrinsic Control”. Available at:
http://www.idthink.net/biot/lexA/index.html.%20Accessed%20on%2001/10/2005.
Secondary Refernces
Johnston, N., (2005). “Reversing the evolution of antibiotic resistance”. Drug Discovery Today. 10;1267
By: Alyssa Firkus
41331444
Antibiotic resistance has been a tremendous hurdle for battling many fatal diseases, such as cancer. Understanding the evolution of antibiotic resistance could further future drug design. Recent studies have shown that random mutations may not be random at all. Bacteria ensure that these mutations happen, "purposeful mutations. These "purposeful mutations" are essential in making sure there is plenty of variability, this is esseantial to form antibiotic resistance. Floyd Romesberg and colleagues tested two antibiotics, ciprofloxacin and rifampicin, to discover that Lex A cleavage is needed for the evolution of resistive, in both antibiotics tested, it causes bacteria not to develop resistance (Gene, 2005). Lex A stops the SOS response, which reacts in the cell when DNA synthesis is inhibited (Gene 2005). The removal of Lex A keeps the cell from being able to adapt. What can this mean for life? What genes can be controlled?
These findings look promising for future drug design, small molecules when administered with antibiotics could prevent bacteria from attaining resistance mutations. (Johnston 2005). Could this fight against antibiotic resistance lead to the reverse of other common resistances? Could this change previous existing resistances?
PrimaryReferences
Gene, M. (2005). “Evolution Under Intrinsic Control”. Available at:
http://www.idthink.net/biot/lexA/index.html.%20Accessed%20on%2001/10/2005.
Secondary Refernces
Johnston, N., (2005). “Reversing the evolution of antibiotic resistance”. Drug Discovery Today. 10;1267
Epigenetics: the Key to Unlocking Schizophrenia
By Jessica Moss
Epigenetics, the study of non-genotype related phenotype variability and inheritance, has lead to increased information about the inheritance and pathophysiology of schizophrenia. The complex psychotic disorder is an irregular genetic disease, characterizing non-mendelian anomalies in heritability.
Research since 1975 has shown high correlation between histone remodelling and methylation, and inheritance patterns and disease function. Renewed research into the field of epigenetics and chromatin structure modification has presented the potential for pharmacological correcting of these epigenetic factors, providing evidence that schizophrenia is partly the result of unregulated epigenetic factors and gene expression.
Comparative twin studies have also shown strong environmental influence on the formation of epigenetic factors, such as DNA methylation and chromatin remodelling, shown to be influential in emergence of the disease. Decreased condensation of chromatin and irregular DNA methylation of important gene promoter sites have also been discovered in schizophrenic patients.
The presence of these expression modifying factors involved in schizophrenia may provide insight to the function and inheritance of the psychotic disorder, and the targets required for future drug development.
Epigenetics, the study of non-genotype related phenotype variability and inheritance, has lead to increased information about the inheritance and pathophysiology of schizophrenia. The complex psychotic disorder is an irregular genetic disease, characterizing non-mendelian anomalies in heritability.
Research since 1975 has shown high correlation between histone remodelling and methylation, and inheritance patterns and disease function. Renewed research into the field of epigenetics and chromatin structure modification has presented the potential for pharmacological correcting of these epigenetic factors, providing evidence that schizophrenia is partly the result of unregulated epigenetic factors and gene expression.
Comparative twin studies have also shown strong environmental influence on the formation of epigenetic factors, such as DNA methylation and chromatin remodelling, shown to be influential in emergence of the disease. Decreased condensation of chromatin and irregular DNA methylation of important gene promoter sites have also been discovered in schizophrenic patients.
The presence of these expression modifying factors involved in schizophrenia may provide insight to the function and inheritance of the psychotic disorder, and the targets required for future drug development.
For more information:
Sharma, R.P. (2005) “Schizophrenia, epigenetics and ligand-activated nuclear receptors: a framework for chromatin therapeutics” Schizophrenia Research 72:79-90
REBELIOUS MICE CAUSE PATCHES IN GENETIC LAWS
A recent study has scientists worldwide re-evaluating the principles of modern genetics in the hope of answering a common question; could RNA contain heritable material?
It has long been accepted that all of the instructions for creating an organism are provided by DNA, with RNA acting purely as an assistant. This idea is currently under review, as evidence has emerged to suggest that RNA may also have some hereditary involvement. A team of French researchers performed an experiment on grey and brown mice, focusing on mutant genes that cause white fur patches to appear. Somewhat inexplicably, they found that mice with homozygous normal genes displayed the mutant phenotype of their heterozygous parents. Affirming the notion of RNA’s hereditary involvement even further was the birth of a patchy mouse from two homozygous wildtype parents. This occurred by injection of RNA stands associated with the mutant genes into the fertilized wildtype egg.
Genetic defects resulting from RNA heritability could rapidly become a thing of the past, as RNA is a relatively unstable molecule and is therefore susceptible to pharmacological attack. Perhaps a comprehensive understanding of genetics is a futuristic prospect, but can we cure disease with epigenetics? Research projects like this (Nature News, http://http://www.nature.com/news/2006/060522/full/news060522-13.html) are the key.
By 41179114
References:
Vardhman K Rakyan, Stephen Beck, 2006, Science Direct: Epigenetic variation and inheritance in mammals
Helen Pearson, 2006, Nature News, Mutant mice challenge rules of genetic inheritance (http://www.nature.com/news/2006/060522/full/news060522-13.html)
It has long been accepted that all of the instructions for creating an organism are provided by DNA, with RNA acting purely as an assistant. This idea is currently under review, as evidence has emerged to suggest that RNA may also have some hereditary involvement. A team of French researchers performed an experiment on grey and brown mice, focusing on mutant genes that cause white fur patches to appear. Somewhat inexplicably, they found that mice with homozygous normal genes displayed the mutant phenotype of their heterozygous parents. Affirming the notion of RNA’s hereditary involvement even further was the birth of a patchy mouse from two homozygous wildtype parents. This occurred by injection of RNA stands associated with the mutant genes into the fertilized wildtype egg.
Genetic defects resulting from RNA heritability could rapidly become a thing of the past, as RNA is a relatively unstable molecule and is therefore susceptible to pharmacological attack. Perhaps a comprehensive understanding of genetics is a futuristic prospect, but can we cure disease with epigenetics? Research projects like this (Nature News, http://http://www.nature.com/news/2006/060522/full/news060522-13.html) are the key.
By 41179114
References:
Vardhman K Rakyan, Stephen Beck, 2006, Science Direct: Epigenetic variation and inheritance in mammals
Helen Pearson, 2006, Nature News, Mutant mice challenge rules of genetic inheritance (http://www.nature.com/news/2006/060522/full/news060522-13.html)
Transposons Can Lead Double Lives
Advancements in genome sequencing support hypothesise that transposons make up large parts of genomes. Numerous examples exist that also support stress induced activation of transposons (Morish et al 2007). Little is known though, how signals induced by stress relay to transposons.
Importantly advancements in position selection for insertions by transposons have been made through work on Ty elements in Saccharomyces cerevisiae. Ty elements are long terminal repeats (LTR) retrotransposons. In Ty5 exists the preference to bind 2 ways.
Firstly, Ty5 can intergrate into heterochromatin, which is tightly packed DNA with limited transcription. When the intergrase of Ty5 is phosphorlated, the interaction between that intergrase and Sir4p, which is an intergral piece of heterochromatin, is stabilized. Experiments have been shown that for the Ty5 to bind the DNA needs to be secured to the Sir4p.
the second binding preference of Ty5 is that it can intergrate into the genome to protect it. When Sir4p is bound to LexA the Ty5 intergrase binds to the lexA protect the gemone. Along with protetion it is possibly to insure that copies of Ty5 are always available.
The possibilty that Ty5 can bind 2 ways possibly means other retrotransposons may do also. It as been proposed therefore from this evidence that the genome may use transposons to rearrange itself when stress is applied.
by Charlie Brunello 41189757
References.
Ebina, H; Levin, H.L. (2007) Stress management: How Cells Take Control of Their Transposons. Cell Press p180-181
Morrish, T.A. Garcia-Peez, J.L., Stamato, T.D., Taccioli, G.E., Sekiguchi, J., and Moran, J.V. (2007) Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres Nature 446, 208-212
Importantly advancements in position selection for insertions by transposons have been made through work on Ty elements in Saccharomyces cerevisiae. Ty elements are long terminal repeats (LTR) retrotransposons. In Ty5 exists the preference to bind 2 ways.
Firstly, Ty5 can intergrate into heterochromatin, which is tightly packed DNA with limited transcription. When the intergrase of Ty5 is phosphorlated, the interaction between that intergrase and Sir4p, which is an intergral piece of heterochromatin, is stabilized. Experiments have been shown that for the Ty5 to bind the DNA needs to be secured to the Sir4p.
the second binding preference of Ty5 is that it can intergrate into the genome to protect it. When Sir4p is bound to LexA the Ty5 intergrase binds to the lexA protect the gemone. Along with protetion it is possibly to insure that copies of Ty5 are always available.
The possibilty that Ty5 can bind 2 ways possibly means other retrotransposons may do also. It as been proposed therefore from this evidence that the genome may use transposons to rearrange itself when stress is applied.
by Charlie Brunello 41189757
References.
Ebina, H; Levin, H.L. (2007) Stress management: How Cells Take Control of Their Transposons. Cell Press p180-181
Morrish, T.A. Garcia-Peez, J.L., Stamato, T.D., Taccioli, G.E., Sekiguchi, J., and Moran, J.V. (2007) Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres Nature 446, 208-212
Plants add a little colour to stress
Natural selection has always favoured those equipped to survive under stressful circumstances. Wether through personal perseverance or through their genetic offspring this often requires flexibility in the organism’s life style/cycles. Plants flowering (and by association reproduction) is usually highly coordinated with specific endogenous and external cues for obvious reasons. Amazingly experiments using Arabidopsis thaliana as a model have shown that under stressful circumstances such as infection and exposure to UV-C light, usual flowering pathways are by-passed and flowering time is accelerated.
When subjected to prolonged UV-C light salicylic acid (SA) accumulates in Arabidopsis thaliana’s system and triggers this phenomenon. NahG transgenic, sid1/eds5 and sid2 plants that cannot increase SA concentration do not display shorting of flowering time. Even more exciting SA has also been linked to plant defense responses, gene expression during leaf senescence, thermogenicity, cell growth, cell death, regulation of FLOWERING LOCUS C and even other regulation of flowering time through different pathways in non-stressed plants!
Aiding survival under extenuating circumstances, the fluctuating levels of SA gives plants an advantage in the earth’s current (past and future) unpredictable environmental conditions. This research also provides room for further investigation and the flexing of young scientists microscopes with the hope of more intriguing discoveries.
When subjected to prolonged UV-C light salicylic acid (SA) accumulates in Arabidopsis thaliana’s system and triggers this phenomenon. NahG transgenic, sid1/eds5 and sid2 plants that cannot increase SA concentration do not display shorting of flowering time. Even more exciting SA has also been linked to plant defense responses, gene expression during leaf senescence, thermogenicity, cell growth, cell death, regulation of FLOWERING LOCUS C and even other regulation of flowering time through different pathways in non-stressed plants!
Aiding survival under extenuating circumstances, the fluctuating levels of SA gives plants an advantage in the earth’s current (past and future) unpredictable environmental conditions. This research also provides room for further investigation and the flexing of young scientists microscopes with the hope of more intriguing discoveries.
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Written by: Christina Harris (41396751)
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Primary Reference
-
Martínez, C, Pons, E, Prats, G & León, J 2004, ‘Salicylic acid regulates flowering time and links defence responses and reproductive development’, The Plant Journal, vol. 37, no. 2, pp. 209–217
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Secondary References
Boss, PK, Bastow, RM, Mylne, JS & Dean, C 2004, ‘Multiple Pathways in the Decision to Flower: Enabling, Promoting, and Resetting (in Flower Development)’, The Plant Cell, vol. 16, pp. S18-S31.
Malamy, J, Carr, JP, Klessig, DF & Raskin, I 1990, ‘Salicylic Acid: A Likely Endogenous Signal in the Resistance Response of Tobacco to Viral Infection’, Science, vol. 250, no. 4983, pp. 1002-1004
Raskin, I, Ehmann, A, Melander, WR, & Meeuse, BJD 1987, ‘Salicylic Acid: A Natural Inducer of Heat Production in Arum Lilies’, Science, vol. 237, no. 4822, pp. 1601-1602.
Sheldon, CC, Rouse, DT, Finnegan, EJ, Peacock, WJ, & Dennis, ES 2000, ‘The Molecular Basis of Vernalization: The Central Role of FLOWERING LOCUS C (FLC)’, Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 7, pp. 3753-3758.
Under Pressure
Scorching solar radiation. Exposure to free radicals. Mutagenic conditions that the cosmetic industry have made us well aware of. They are also examples of mutagenic conditions that affect bacterial DNA, initiating something called the SOS response. This mechanism is involved in nucleotide excision repair and recombinational repair. In the latter situation, it is their final chance for survival under harmful conditions, with badly damaged DNA being repaired by error-prone DNA polymerase. The objective is that at least one member of the struggling population will acquire a mutation to overcome the new deleterious environment. These conditions were thought to be only those conducive to DNA damage, such as UV light, and exposure to mutagenic chemicals. It now appears, however, that a non-mutagenic physical stress can also stimulate the same pathway of last resort.
In a study conducted by Aertson et al. (2005), hydrostatic pressure was applied to Escherichia coli. Amazingly, it was found that this non-mutagenic stress also initiated the SOS response. A novel cellular response is induced in response to a stress that cannot thermodynamically affect DNA integrity. Through further study of the SOS regulon, it is hoped that we may one day have a means of overcoming antibiotic resistant bacteria, which threatens to be a huge global problem.
Merran Neilsen
41203952
Primary Reference
Aertsen.A, Michiels..C.W. 2005 Mrr stimulates the SOS response after high pressure stress in escherichia coli. Journal of Molecular Microbiology. 58.5. 1381-1391.
Hungry Transposons
Transposons for a long time have been integrated themselves into the genomes of their hosts, especially in bacteria like an unwanted guest living in your house. These nomadic sequences have fixated themselves in the host and appear in high frequency when it encounters certain external stimuli. It has been shown that different environmental stresses, such as radiation, temperature and starvation have increased the activity of transpositional elements. However these unwanted houseguest’s aren’t just occupying space, they can enhance the survival of their host when face with a life threatening stress by increasing its genetic variability.
Tn4652 is a 17kb stationary phase specific transposase promoter that occupies PaW85 strains of Pseudomonas putida. Studies of P. putida in starving conditions on phenol plates have shown how mutant strains have activated promoter-less phenol degradation genes in the plasmid pEST1414. The insertion of this element upstream from the target DNA created a fusion promoter that is coincidently activated by physiological stress. The longer the time of starvation was the higher the frequency of the Tn4652. This is the first time a direct stationary phase specific regulation of a mobile element transposase. Truly these transpositional elements aren’t the worst things to be hosts for.
Primary references:
ILVES, H., R. HORAK, and M. KIVISAAR, 2001 Involvement of {sigma}S in starvation-induced transposition of Pseudomonas putida transposon Tn4652.. J. Bacteriol. 183:5445-5448. [online] Available at: http://jb.asm.org/cgi/content/abstract/183/18/5445 (accessed on 8/10/07)
Secondary reference:
Capy, P., G. Gasperi, C. Biemont, and C. Bazin. 2000. Stress and transposable elements: co-evolution or useful parasites? Heredity 85:101-106. [online] Available at: http://www.blackwell-synergy.com/doi/ref/10.1046/j.1365-2540.2000.00751.x?cookieSet=1 (accessed on 8/10/07)
by 41207192
Tn4652 is a 17kb stationary phase specific transposase promoter that occupies PaW85 strains of Pseudomonas putida. Studies of P. putida in starving conditions on phenol plates have shown how mutant strains have activated promoter-less phenol degradation genes in the plasmid pEST1414. The insertion of this element upstream from the target DNA created a fusion promoter that is coincidently activated by physiological stress. The longer the time of starvation was the higher the frequency of the Tn4652. This is the first time a direct stationary phase specific regulation of a mobile element transposase. Truly these transpositional elements aren’t the worst things to be hosts for.
Primary references:
ILVES, H., R. HORAK, and M. KIVISAAR, 2001 Involvement of {sigma}S in starvation-induced transposition of Pseudomonas putida transposon Tn4652.. J. Bacteriol. 183:5445-5448. [online] Available at: http://jb.asm.org/cgi/content/abstract/183/18/5445 (accessed on 8/10/07)
Secondary reference:
Capy, P., G. Gasperi, C. Biemont, and C. Bazin. 2000. Stress and transposable elements: co-evolution or useful parasites? Heredity 85:101-106. [online] Available at: http://www.blackwell-synergy.com/doi/ref/10.1046/j.1365-2540.2000.00751.x?cookieSet=1 (accessed on 8/10/07)
by 41207192
Complex trait analysis: scampering along!
Mouse and other mammalian genes with interesting phenotypic variation are determined mainly by quantitative trait loci (QTL). Identifying these complex and quantitative traits remains extremely difficult, although methods and resources are rapidly improving. In his paper Shalkwyk discusses many approaches to identify the genes for traits including using QTL mapping of inbred strains. However inbreeding increases the amount of recombination in the animals. During inbreeding some become fixed either from homozygous individuals or by genetic drift. To reduce drift, short term selection may be a viable alternative to extended inbreeding programs. A traditional approach to genetic mapping is to cross two inbred strains and backcross one of the F1 with one of the parental strains to produce F2 generation which are then phenotyped. Shalkwyk also discusses the use of Genetic Reference Populations(GRP), which allows data to be aggregated amongst labs through time, and Recombinant Inbred (RI) panels or a combination of both as possibly having huge potentials for locating genes and their potential for causing phenotypic variance. RI panels allows for testing across a range of environments using as many replicates as needed on test-naïve individuals. Recently two large RI panels have become available which improves the ability to detect QLT of small effect.
If you're interested click here
Schalkwyk, L.C. 2005. Complex trait approaches to the analysis of behaviour in the mouse. Psychiatry 12: 18-21
Epigenetic control of plant development.
For the past few decades, R.M. Amasino and his team have rigorously pursued the study of epigenetic control in plants, that is control of gene expression through systems which do not involve altering of the genetic sequence itself. Examples of this included binding of proteins to DNA to block or inhibit transcription taking place, or mechanisms which effect the post-transcriptional processing of mRNA transcripts (differental intron splicing, polyadenlation etc.). The focus of research has been upon the vernalization mechanism or how plants respond to a period of cold weather ie. winter as a signal to switch from vegetative development (plant growth) to reproductive develpment (production of flower structures). Using the ubiquitous Aribidopsis thaliana as a model organism for study of these processes, Amasino and co. identified several key genes involved in this process, one of which, the Flowering Locus C (FLC) has been discussed in great depth.
A breakthrough in this research occured in 2003, when Amasino identified two keen genes which were found to interact with and regulate the expression of FLC, FY and FCA. However these two genes do not function in the vernalization as such, instead they play a role in the autonomous reguation pathway, which seems to have been misconstrued by some of my peers. The focus of Amasino's research is not primarily on elucidating the mechanism of vernalization, but on epigenetics and studying how this regulation works, I think with an aim for extrapolation from plants to the study of genetics across Eukaryota.
It is in a later paper (Schmitz 2007), Amasino discusses the genetics of vernalization with greater specificity, almost with vernalization as an end in itself if you will. He shows that many genes are involved in vernalization, again with FLC as the central figure in this mechanism, forming the vernalization switch if you will.
The work in 2003, I found to be most interesting. The hypothesis of an FCA-FY complex not only regulating expression of FLC, supressing and hence promoting florescence, but also its potential function in its own regulation, and while this connection still hasnt been fully elucidated or proven, it seemed to be plausible and Amasino argued fr it quite convincingly I felt. I'm looking forward to future study in this area, something I would be highly entusiastic to be involved in myself, in really tying down this mechansim in a detailed way to a molecular level. Research in this area, would I feel have great potential in controlling harvest and improving crop yield efficency if we can get a handle on this whole vernalization pathway.
References
Schmitz RJ, Amasino RM; Vernalization: A model for investigating epigenetics and eukaryotic gene regulation in plants; BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1769 (5-6): 269-275 MAY-JUN 2007.
Amasino RM; Flowering time: A pathway that begins at the 3 ' end; CURRENT BIOLOGY 13 (17): R670-R672 SEP 2 2003.
A breakthrough in this research occured in 2003, when Amasino identified two keen genes which were found to interact with and regulate the expression of FLC, FY and FCA. However these two genes do not function in the vernalization as such, instead they play a role in the autonomous reguation pathway, which seems to have been misconstrued by some of my peers. The focus of Amasino's research is not primarily on elucidating the mechanism of vernalization, but on epigenetics and studying how this regulation works, I think with an aim for extrapolation from plants to the study of genetics across Eukaryota.
It is in a later paper (Schmitz 2007), Amasino discusses the genetics of vernalization with greater specificity, almost with vernalization as an end in itself if you will. He shows that many genes are involved in vernalization, again with FLC as the central figure in this mechanism, forming the vernalization switch if you will.
The work in 2003, I found to be most interesting. The hypothesis of an FCA-FY complex not only regulating expression of FLC, supressing and hence promoting florescence, but also its potential function in its own regulation, and while this connection still hasnt been fully elucidated or proven, it seemed to be plausible and Amasino argued fr it quite convincingly I felt. I'm looking forward to future study in this area, something I would be highly entusiastic to be involved in myself, in really tying down this mechansim in a detailed way to a molecular level. Research in this area, would I feel have great potential in controlling harvest and improving crop yield efficency if we can get a handle on this whole vernalization pathway.
References
Schmitz RJ, Amasino RM; Vernalization: A model for investigating epigenetics and eukaryotic gene regulation in plants; BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1769 (5-6): 269-275 MAY-JUN 2007.
Amasino RM; Flowering time: A pathway that begins at the 3 ' end; CURRENT BIOLOGY 13 (17): R670-R672 SEP 2 2003.
The mysterious role of Heat shock proteins in Evolutions
Hsp are important family of proteins that buffer mutations, protect proteins against stresses and missfolding. Hsp let the organism to accumulate new mutations over the time without permitting to transcribe them. They are abundant in normal temperatures but highly induced by stress. Hsp, under certain conditions, interact with highly selected unstable proteins like kinases and transcription factors and signal transduction. Any mutation in these proteins leads to remarkable alteration in the developmental pathways.
However variation in nature indicates mutations’ occurrence!
Hsp could not protect against mutations until one of two circumstances occur; the concentration of mutations is high and if environment conditions change rapidly.
Studies found out that Hsp have a limited capacity to hold mutations but after that mutations would be expressed in the organism. Mutations also develop in fruit flies when exposed to high and low temperatures even with a normal HSP90 gene. So the hidden mutations in the flies turn up in harsh conditions to change fly’s proteins and phenotype.
Alternatively, some masked mutations and multiple polymorphisms become independent of Hsp if enriched by selection. The continuous selection of these traits would lead to continuous variation of them even thought if Hsp are functioning. This situation brings some cryptic questions about the limits of Hsp and what types of mutations they buffer and do Hsp accumulate then release mutations or just buffer them? Were Hsp absent in certain times then revealed? How efficient are they? Can they buffer all mutations or just selected types of them?
One probable answer might be certain; these proteins played important role in evolution history and need to be more investigated.
student # 40890618
References:
Pennisi, E 1998. ‘Heat Shock Protein Mutes Genetic Changes’, Science, New Series, Vol. 282, No. 5395, p. 1796.
Suzanne, Rutherford & Lindquist 1998. ‘Hsp90 as a capacitor for morphological evolution’, Nature, Vol. 396, No 6709, p.336-342.
Queitsch, Sangster & Lindquist 2002. ‘Hsp90 as a capacitor of phenotypic variation’, Nature 417, No. 6889, p. 618-624.
However variation in nature indicates mutations’ occurrence!
Hsp could not protect against mutations until one of two circumstances occur; the concentration of mutations is high and if environment conditions change rapidly.
Studies found out that Hsp have a limited capacity to hold mutations but after that mutations would be expressed in the organism. Mutations also develop in fruit flies when exposed to high and low temperatures even with a normal HSP90 gene. So the hidden mutations in the flies turn up in harsh conditions to change fly’s proteins and phenotype.
Alternatively, some masked mutations and multiple polymorphisms become independent of Hsp if enriched by selection. The continuous selection of these traits would lead to continuous variation of them even thought if Hsp are functioning. This situation brings some cryptic questions about the limits of Hsp and what types of mutations they buffer and do Hsp accumulate then release mutations or just buffer them? Were Hsp absent in certain times then revealed? How efficient are they? Can they buffer all mutations or just selected types of them?
One probable answer might be certain; these proteins played important role in evolution history and need to be more investigated.
student # 40890618
References:
Pennisi, E 1998. ‘Heat Shock Protein Mutes Genetic Changes’, Science, New Series, Vol. 282, No. 5395, p. 1796.
Suzanne, Rutherford & Lindquist 1998. ‘Hsp90 as a capacitor for morphological evolution’, Nature, Vol. 396, No 6709, p.336-342.
Queitsch, Sangster & Lindquist 2002. ‘Hsp90 as a capacitor of phenotypic variation’, Nature 417, No. 6889, p. 618-624.
Anti-antibiotic-resistance
A recent experiment has shown promise with understanding and controlling the mechanisms behind developing antibiotic-resistant bacteria. Many patients and doctors are concerned with the idea of bacteria developing resistance to antibiotics; a new drug which could prevent bacteria from ever preventing resistance to antibiotics would vastly decrease the risk of patients developing bacterial infections to a life threatening level.
Since the 1970’s, scientists have been aware of a practice, known as the SOS response, in bacteria. The bacteria utilize mutations, which are usually associated as a form of malfunction of DNA replication, as a method of self-preservation. A molecular biologist by the name of Floyd E. Romesberg fronted a team of scientist in an experiment to further our understanding of the SOS response in bacteria. After discovering the mechanisms employed by bacteria to develop resistance, Romesberg saw the opportunity to develop a pharmaceutical drug which could increase the efficiency of antibiotics. Romesberg, at his laboratory at the Scripps Research Institute in La Jolla, California, leads a group of scientists advancing our knowledge of this subject, as well as studying other ideas concerning evolution. 41190052.
Uncleavable Lex A – E. coli’s Kryptonite
Earlier this year American scientists discovered that the repressor protein Lex A, involved in SOS regulation of enteropathogenic Escherichia coli, also plays a part in mediating the Type III secretion system responsible for causing watery diarrhoea.[1]
This Type III secretion system is responsible for causing attaching and effacing intestinal lesions, which in turn lead to watery diarrhoea. The disease in found primarily in developing countries and can have drastic effects due to water and electrolyte loss in already malnutritioned children.
Jay Mellies and his colleagues discovered that enteropathogenic Escherichia coli that contained a mutation encoding for an uncleavable Lex A protein showed reduced secretions and thus reduced pathogenicity.
In 2005 the same protein was found to be responsible for inducing mutations during SOS response in E. coli following specific antibiotic pressures.[2] It was found that mutant E. coli strains containing an uncleavable Lex A protein were unable to induce mutations and thus unable to acquire antibiotic resistance. This means that by rendering E. coli unable to cleave Lex A they have decreased virulence factors and a malfunction in producing mutations that may allow them to become resistant to antibiotics. It is like exposing Superman to Kryptonite,[3] we can make them weak and unable to use their superpowers.
References:
1 Mellies, J.L. et al. (2007) SOS Regulation of the Type III Secretion System of Enteropathogenic Escherichia coli, Journal of Bacteriology, April, p. 2863-2872
2 Cirz, R.T. et al. (2005) Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biology 3, e176
3 http://site.supermanthrutheages.com/Encyclopaedia/kryptonite.php (accessed on 9/10/07)
This blog was written by Ivana Ferreira 41214631
This Type III secretion system is responsible for causing attaching and effacing intestinal lesions, which in turn lead to watery diarrhoea. The disease in found primarily in developing countries and can have drastic effects due to water and electrolyte loss in already malnutritioned children.
Jay Mellies and his colleagues discovered that enteropathogenic Escherichia coli that contained a mutation encoding for an uncleavable Lex A protein showed reduced secretions and thus reduced pathogenicity.
In 2005 the same protein was found to be responsible for inducing mutations during SOS response in E. coli following specific antibiotic pressures.[2] It was found that mutant E. coli strains containing an uncleavable Lex A protein were unable to induce mutations and thus unable to acquire antibiotic resistance. This means that by rendering E. coli unable to cleave Lex A they have decreased virulence factors and a malfunction in producing mutations that may allow them to become resistant to antibiotics. It is like exposing Superman to Kryptonite,[3] we can make them weak and unable to use their superpowers.
References:
1 Mellies, J.L. et al. (2007) SOS Regulation of the Type III Secretion System of Enteropathogenic Escherichia coli, Journal of Bacteriology, April, p. 2863-2872
2 Cirz, R.T. et al. (2005) Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biology 3, e176
3 http://site.supermanthrutheages.com/Encyclopaedia/kryptonite.php (accessed on 9/10/07)
This blog was written by Ivana Ferreira 41214631
Direcetd Evolution - SOS Response: One Individual Really Could Make a Difference
One Individual Really Could Make a DifferenceLaura Norton 4100741
As antibiotic resistance is a growing problem, the means by which bacteria produce resistance need to be thoroughly understood in order to combat it. The SOS response is known to be responsible for generating adaptive mutations and resistance in bacteria, which is why understanding this mechanism could be the key to reducing or eliminating antibiotic resistance.
Whole populations of Escherichia coli’s SOS Response have been examined, but Friedman et al. (2005) have shown that the individual cell’s response is quite different to the response of the population. They studied the SOS genes by the use of a green fluorescent protein as a reporter for the promoter activity of the response after activation by ultraviolet irradiation. They found that in individual cells, the SOS response exhibits very structured and discrete activation peaks which have precise timing. The peaks correlate with the cell’s growth rate, but not with the stage in the cell cycle. They found that the number of peaks increases with UV dose, their timing is constant and their amplitude reaches saturation.
This study shows the importance of looking at individual cells to see exactly what is happening in the response, as a nonhomologous population can mask individual effects.
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pbio.0030238
Reference
Friedman, N, Alon, U, Ronen, M, Stavans, J and Vardi, A 2005, ‘Precise temporal modulation in the response of the SOS DNA repair network in individual bacteria’, PLoS Biology, vol. 3, no. 7, pp. 1261 – 1268.
Epigenetics and Evolution in Mammals: The Evidence Rakyan and Beck Should Have Used
Evidence that epigenetics can be involved in evolution has been demonstrated by Crews et al. They have shown that an inherited epigenetic mutation i.e. DNA methylation, influences sexual selection in rats, thus impacting on evolution. Exposure to the fungicide vinclozolin, an endocrine-disrupting chemical, causes a mutation within the epigenome that leads to a disease phenotype in successive generations of offspring. Tests were conducted using rats from a lineage that was three generations removed from the original generation that was treated with vinclozolin. Both treated and untreated female rats showed a significant preference towards untreated male rats vs. treated male rats. These results were shown to occur prior to the onset of the disease phenotype and it was not found how the female rats were able to distinguish between treated and untreated males. The type of sexual selection that these rats demonstrated was female preference. Female preference has long been recognised as a mechanism of evolution. For example, female choice is the main mechanism of evolution of extreme tail length in the male widowbird (Andersson 1982). Female choice in the rat population selected against the disease phenotype, based on the presence or absence of an epigenetic mutation.
By: 41195105
References
Main Article: Crews D, et al 2007 "Transgenerational epigenetic imprints on mate preference" PNAS. vol. 104, no. 14, pp. 5942-5946
Secondary Link: Andersson M, 1982 "Female choice selects for extreme tail length in a widow bird" Nature, no. 299, pp. 818-820
By: 41195105
References
Main Article: Crews D, et al 2007 "Transgenerational epigenetic imprints on mate preference" PNAS. vol. 104, no. 14, pp. 5942-5946
Secondary Link: Andersson M, 1982 "Female choice selects for extreme tail length in a widow bird" Nature, no. 299, pp. 818-820
Importance of SOS Response to Antibiotic Resistance
New antibiotics are constantly being devised to overcome a major problem in today’s society, that is drug resistance. In response, bacteria are continually evolving new ways around these antibiotics, resulting in ineffectiveness of treatment. DNA damage is caused by many factors including antibiotics, DNA polymerases, and UV radiation, which activate the SOS response, an inducible, DNA repair system.
The SOS response uses the RecA inducer protein stimulated by single-stranded DNA that is caused by damage, to inactivate the LexA repressor protein, inducing the response. Presence of the LexA protein represses the SOS response, inhibiting or limiting DNA repair, and resulting in resistance to the antibiotic.
The SOS response has played a significant role in the bacterial world, inducing mutations and genetic exchanges. Recent studies have shown that the SOS pathway may be vital in the acquisition of bacterial mutations, which lead to antibiotic resistance.
Staphylococcus aureus, a gram-positive pathogen, is unique in its ability to easily acquire multidrug resistance, and its incredible ability to persist and adapt. To determine how this pathogen persists when exposed to antibiotics, a study by Cirz et al, in 2007 observed its response to the antibiotic ciprofloxacin. When the DNA is damaged by ciprofloxacin, RecA binds to the damaged, single-stranded DNA as well as the repressor gene LexA. This cleavage inactivates the LexA gene, resulting in induction of the SOS genes. Therefore, this shows that the SOS response actually facilitates survival and evolution of resistance, by inducing mutation.
Primary reference:
Cirz, R.T., Chin, J.K., Andes, D.R., Crecy-Lagard, V., Craig, W.A., Romesberg, F,E. (2005). Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biology 3(6): 1024-1033.
Secondary references:
Cirz, R.T., Jones, M.B., Gingles, N.A., Minogue, T.D., Jarrahi, B. Peterson, S.N., Romesberg, F.E. (2007). Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin. Journal Of Bacteriology 189(2): 531-539.
McKenzie, G.J., Harris, R. S., Lee, P.L., Rosenberg, S.M. (2000). The SOS response regulates adaptive mutation. PNAS 97(12): 6646-6651.
Michel, B. (2005). After 30 Years of Study, the bacterial SOS Response Still Surprises Us. PloS Biology 3(7): e255 doi:10.1371/journal.pbio.0030255
Posted by: 4139260
The SOS response uses the RecA inducer protein stimulated by single-stranded DNA that is caused by damage, to inactivate the LexA repressor protein, inducing the response. Presence of the LexA protein represses the SOS response, inhibiting or limiting DNA repair, and resulting in resistance to the antibiotic.
The SOS response has played a significant role in the bacterial world, inducing mutations and genetic exchanges. Recent studies have shown that the SOS pathway may be vital in the acquisition of bacterial mutations, which lead to antibiotic resistance.
Staphylococcus aureus, a gram-positive pathogen, is unique in its ability to easily acquire multidrug resistance, and its incredible ability to persist and adapt. To determine how this pathogen persists when exposed to antibiotics, a study by Cirz et al, in 2007 observed its response to the antibiotic ciprofloxacin. When the DNA is damaged by ciprofloxacin, RecA binds to the damaged, single-stranded DNA as well as the repressor gene LexA. This cleavage inactivates the LexA gene, resulting in induction of the SOS genes. Therefore, this shows that the SOS response actually facilitates survival and evolution of resistance, by inducing mutation.
Primary reference:
Cirz, R.T., Chin, J.K., Andes, D.R., Crecy-Lagard, V., Craig, W.A., Romesberg, F,E. (2005). Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biology 3(6): 1024-1033.
Secondary references:
Cirz, R.T., Jones, M.B., Gingles, N.A., Minogue, T.D., Jarrahi, B. Peterson, S.N., Romesberg, F.E. (2007). Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin. Journal Of Bacteriology 189(2): 531-539.
McKenzie, G.J., Harris, R. S., Lee, P.L., Rosenberg, S.M. (2000). The SOS response regulates adaptive mutation. PNAS 97(12): 6646-6651.
Michel, B. (2005). After 30 Years of Study, the bacterial SOS Response Still Surprises Us. PloS Biology 3(7): e255 doi:10.1371/journal.pbio.0030255
Posted by: 4139260
Hsp90 as an agent to control evolvability
Hsp90 suppression can cause novel morphologies in Drosophila and Arabidopsis, yet research so far has mainly looked at the qualitative traits which are affected. Recently some research was done to see how it can effect the smaller quantitative traits which are more important or more effective for evolution. It was found that Hsp90 only affected some very specific quantitative traits which tended to be invariable and very discrete.
The fact that the traits shown when Hsp90 expression is reduced depends on the genetic background of the flies is evidence that the traits evolve separately and are then released when Hsp90 stops its buffering effect. Bristle number and scutellor mutations are threshold traits like the qualitative mutations buffered by Hsp90. It was found that a wide range of responses are buffered more strongly whilst a narrower range of mutations can more easily break down the Hsp90 buffer and become independent or 'fixed' into the population.
While Hsp90 can cause an increase in heritability and evolvability of a genotype in a population, the effects for an individual cannot be controlled, so use of Hsp90 suppression as a tool for evolution would likely be a last hope grasp for evolution, as many of the individuals in the population would die from the mutations that occur, or become significantly less fit.
posted by 41171323
Controlling flowering time in Arabidopsis
Posttranscriptional regulation is important in the controlling of flowering time in Arabidopsis. FCA gene product like an RNA binding protein and the other processes of FCA transcript shows that posttranscriptional regulation is important. The RNA binding proteins function in processing like, splicing, nuclear export, RNA stability, translation and polyadenylation.
WW protein – protein interaction displays that FCA also interacts with other proteins, like with proline-rich ligand. fca-1 mutations shows that this protein is important for FCA function. WW containing proteins functions to bring proteins together intracellular in regulatory pathways. Knowing which proteins bind to the FCA WW domain will help to find out what the function of the domain is in the FCA protein.
Experimental data shows that transcript y shows that it is the only transcript that encodes a functional FCA protein. FCA transcript is spliced and four mRNAs were detected, suggesting that FCA is a component of the posttranscriptional regulatory cascade. When the transcription of the FCA gene was increased, very high amount of transcript β levels, small increases in transcript y and δ levels resulted in an acceleration in flowering time. The flowering time of the 35S-FCA was ealier than the wild type. This may have been due to the fact there was an increase in levels of transcript y.
In conclusion FCA functions in the posttranscriptional regulation of transcripts that were involved in flowering process. The plants that had the FCA gene, which was fused to the 35S promoter flowered earlier, also the ratio and the concentration of the different FCA transcripts were changed. FCA is a component of the posttranscriptional cascade that is involved in th econtrol of flowering time in Arabidopsis.
posted by student: 41283132
WW protein – protein interaction displays that FCA also interacts with other proteins, like with proline-rich ligand. fca-1 mutations shows that this protein is important for FCA function. WW containing proteins functions to bring proteins together intracellular in regulatory pathways. Knowing which proteins bind to the FCA WW domain will help to find out what the function of the domain is in the FCA protein.
Experimental data shows that transcript y shows that it is the only transcript that encodes a functional FCA protein. FCA transcript is spliced and four mRNAs were detected, suggesting that FCA is a component of the posttranscriptional regulatory cascade. When the transcription of the FCA gene was increased, very high amount of transcript β levels, small increases in transcript y and δ levels resulted in an acceleration in flowering time. The flowering time of the 35S-FCA was ealier than the wild type. This may have been due to the fact there was an increase in levels of transcript y.
In conclusion FCA functions in the posttranscriptional regulation of transcripts that were involved in flowering process. The plants that had the FCA gene, which was fused to the 35S promoter flowered earlier, also the ratio and the concentration of the different FCA transcripts were changed. FCA is a component of the posttranscriptional cascade that is involved in th econtrol of flowering time in Arabidopsis.
posted by student: 41283132
We Are What Our Grandparents Ate??
Written by Mary Lor 41214752
It has always been said; “we are what we eat” this is true of course, as what we eat affects our health and performance for the rest of our lives. But what if, what our grandparents ate and experienced during their lifetimes, affect how we are as well?
Interestingly, scientists now believe that this might in fact, be true. Studies have shown that pregnant mothers living under harsh starvation conditions gave birth to relatively small babies. When they grew up and had children, they were also unexpectedly small, which indicates that poor nutrition can be inherited from generation to generation. But how is this possible? Nutrition cannot be genetically inherited. Scientists believe that this can be explained by the phenomenon: epigenetics, which describes that there are ‘hidden influences’ on phenotypes such as nutritional health, that doesn’t affect or alter the genome that is inherited.
Somehow, our genes have ‘memories’ imprinted on them, which our progeny inherits and then pass through generations. Scientists believe that these ‘memories’ can include anything from what we eat to our life experiences of diseases and disorders. Although this does explain all the mysterious reasons why we are what we are and why we are more susceptible to some diseases than others, how do we know if there are really ‘hidden influences’ that affect us?
Scientists are still struggling to uncover the truth on this mysterious phenomenon of epigenetics.
Primary Reference:
C. Dennis, ‘Epigenetics and disease: Altered states’, Nature 421, 686 – 688 (2003)
Secondary Reference:
J. M. Levenson, J. D. Sweatt, ‘Epigenetic mechanism in memory formation’ Nature Reviews Neuroscience 6, 108-118 (2005)
It has always been said; “we are what we eat” this is true of course, as what we eat affects our health and performance for the rest of our lives. But what if, what our grandparents ate and experienced during their lifetimes, affect how we are as well?
Interestingly, scientists now believe that this might in fact, be true. Studies have shown that pregnant mothers living under harsh starvation conditions gave birth to relatively small babies. When they grew up and had children, they were also unexpectedly small, which indicates that poor nutrition can be inherited from generation to generation. But how is this possible? Nutrition cannot be genetically inherited. Scientists believe that this can be explained by the phenomenon: epigenetics, which describes that there are ‘hidden influences’ on phenotypes such as nutritional health, that doesn’t affect or alter the genome that is inherited.
Somehow, our genes have ‘memories’ imprinted on them, which our progeny inherits and then pass through generations. Scientists believe that these ‘memories’ can include anything from what we eat to our life experiences of diseases and disorders. Although this does explain all the mysterious reasons why we are what we are and why we are more susceptible to some diseases than others, how do we know if there are really ‘hidden influences’ that affect us?
Scientists are still struggling to uncover the truth on this mysterious phenomenon of epigenetics.
Primary Reference:
C. Dennis, ‘Epigenetics and disease: Altered states’, Nature 421, 686 – 688 (2003)
Secondary Reference:
J. M. Levenson, J. D. Sweatt, ‘Epigenetic mechanism in memory formation’ Nature Reviews Neuroscience 6, 108-118 (2005)
Reversing Epigenetics to Treat Cancer
Epigenetics refers to the inheritance of phenotypes through means other than through the genomic sequence. Epigenetic changes affect an individual’s phenotype by altering the chromatin via means of DNA methylation, histone methylation or acetylation, chromatin reshaping and RNA directed alterations (Rakyan and Beck, 2006).
Written by: 41211724
References:
Gender- is it really the primay factor of mammalian growth?
The mouse is a primary model that has been used extensively to study the genetics of
growth, and other cellular functions, in mammals. One of the primary objectives of the genetic analysis of mammal growth is to understand its genetic architecture, that is the number and position of loci affecting the trait, the magnitude of their effects, allele frequencies and types
of gene action. Selection experiments have revealed the existence of strong genetic correlations among traits that were indicative of the complexity of growth regulation at both physiological and genetic levels. Targeted gene deletions (gene knockouts) and transgenics are two methods
growth, and other cellular functions, in mammals. One of the primary objectives of the genetic analysis of mammal growth is to understand its genetic architecture, that is the number and position of loci affecting the trait, the magnitude of their effects, allele frequencies and types
of gene action. Selection experiments have revealed the existence of strong genetic correlations among traits that were indicative of the complexity of growth regulation at both physiological and genetic levels. Targeted gene deletions (gene knockouts) and transgenics are two methods
of characterizing the function of a gene which follow opposite strategies. Adult mice with two copies of the disrupted gene were 30% larger than control mice and, in addition to their more rapid growth, females had impaired maturation of ovarian follicles. Therefore, the results pertaining to QTL mapping experiments for growth suggest that genetic factors regulating growth can be related to the gender of the mouse. Although this selection experiment produced a large amount of information pertaining to the genetic regulation of growth, the nature of this experiment, based on mass selection schemes, precluded the identification of individual genes.
Written by student 41202414
References:
Susanna Wang; Nadir Yehya; Eric E Schadt; Hui Wang; Thomas A Drake; and Aldons J. Lusis PLoS Genet. 2006, February 2. Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity
Pablo M. Corva, Juan F. Medrano- November 28, 2000
Quantitative Trait Loci (QTLs) mapping for growth traits in the mouse: A review
Written by student 41202414
References:
Susanna Wang; Nadir Yehya; Eric E Schadt; Hui Wang; Thomas A Drake; and Aldons J. Lusis PLoS Genet. 2006, February 2. Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity
Pablo M. Corva, Juan F. Medrano- November 28, 2000
Quantitative Trait Loci (QTLs) mapping for growth traits in the mouse: A review
Flies in disguise
Scientists have recently discovered that Drosophila melanogaster, also known as the Fruit Fly, has been accumulating hidden genetic variation. The protein responsible for this is heat shock protein 90 (Hsp90). Scientists have labelled it as an ‘evolutionary capacitor’, meaning that under normal conditions, Hsp90 buffers this genetic variation in D. melanogaster, inhibiting the introduction of both genetic and physical variation.
Scientists originally had the assumption that Hsp90’s only function was to buffer the effect of environmental stresses on D. melanogaster, but they were wrong. This assumption changed when the Hsp90 gene of D. melanogaster was ‘knocked out’. When this was achieved, it introduced flies with phenotypic (physical) variance, never seen before. Further experiments that involved ‘knocking out’ other genes have shown that they too, may have the potential to be evolutionary capacitors.
This suggests that Hsp90 might just be part of a large class of genes with the ability to act as evolutionary capacitors, which complement each other. These set of genes may influence the ability for organisms to adapt, even when not opposed by extreme environmental stress, for example, for sexual selection and predator-prey purposes.
Written by: 41202021
Primary reference:
Bergman, A, Siegal, ML 2003, ‘Evolutionary capacitance as a general feature of complex gene networks’, Nature, vol. 424, pp. 549-552.
Link:http://www.nsm.uh.edu/~dgraur/ArticlesPDFs/popbio2005/bergmansiegalcapacitance2003.pdf
Secondary reference:
Pigliucci, M 2002, ‘Buffer Zone’, Nature, vol. 417, pp. 598-599.
Link:http://bioinformatics.bio.uu.nl/BINF/pdf/Pigliucci.n02.pdf
Scientists have recently discovered that Drosophila melanogaster, also known as the Fruit Fly, has been accumulating hidden genetic variation. The protein responsible for this is heat shock protein 90 (Hsp90). Scientists have labelled it as an ‘evolutionary capacitor’, meaning that under normal conditions, Hsp90 buffers this genetic variation in D. melanogaster, inhibiting the introduction of both genetic and physical variation.
Scientists originally had the assumption that Hsp90’s only function was to buffer the effect of environmental stresses on D. melanogaster, but they were wrong. This assumption changed when the Hsp90 gene of D. melanogaster was ‘knocked out’. When this was achieved, it introduced flies with phenotypic (physical) variance, never seen before. Further experiments that involved ‘knocking out’ other genes have shown that they too, may have the potential to be evolutionary capacitors.
This suggests that Hsp90 might just be part of a large class of genes with the ability to act as evolutionary capacitors, which complement each other. These set of genes may influence the ability for organisms to adapt, even when not opposed by extreme environmental stress, for example, for sexual selection and predator-prey purposes.
Written by: 41202021
Primary reference:
Bergman, A, Siegal, ML 2003, ‘Evolutionary capacitance as a general feature of complex gene networks’, Nature, vol. 424, pp. 549-552.
Link:http://www.nsm.uh.edu/~dgraur/ArticlesPDFs/popbio2005/bergmansiegalcapacitance2003.pdf
Secondary reference:
Pigliucci, M 2002, ‘Buffer Zone’, Nature, vol. 417, pp. 598-599.
Link:http://bioinformatics.bio.uu.nl/BINF/pdf/Pigliucci.n02.pdf
Flowering Plants: Time will tell
Plants ability to produce flowers at the same time year-in-year-out has fascinated botanists and scientists alike for many years. The processes by which this is achieved are still not completely understood, though advances in technology are producing some exciting discoveries.
The three main pathways that have so far been discovered to be involved in the flowering process are; the photoperiod pathway (light intensity and day length), vernalization (temperature sensitive), and autonomous pathway (not affected by environmental conditions). Both the photoperiod pathway and vernalisation are examples of non-autonomous pathways and use environmental cues to regulate flowering time.
The photoperiod pathway is able to stimulate flowering by detecting increasing day length and inducing the expression of a flowering locus. In Arabidopsis it is believed that increased day length, detected by the photoreceptors, stimulate the activation of signalling proteins. Higher levels of these proteins have been found in Arabidopsis in longer days compared to short, which in turn up regulates the expression of a flowering locus and induces flowering.
Work carried out by Yavonsky and Kay, have shown that Arabidopsis with mutant circadian genes are still able to regulate flowering time when exposed to longer ‘day’ length, indicating that flowering can be controlled even if internal mechanisms are faulty.
For more information click here
Toby Mitchell (41450550)
References
Yanovsky, M. J. & Kay, S. A. (2002) – ‘Molecular basis of seasonal time measurement in Arabidopsis’, Nature, 419:308-312
Amasino, R. M. (2003) – ‘Flowering Time: A Pathway that Begins at the 3’ End’, Current Biology, 13:670-672
Fast Track Evolution
As environmental conditions change organisms have to either change with them or face extinction. The ability of an organism to adapt is often the deciding factor on weather or not it will survive in a new or changing habitat. Having a storehouse of genetic mutations is an evolutionary failsafe against extinction. Hsp90 stores genetic mutations in the DNA with out letting them be expressed in the phenotype. This keeps a working phenotype expressed while other possibilities are hidden. As conditions change and Hsp90 is inhibited by stress, a flood of new phenotypes are expressed with the hope that one with a better capability to survive is exposed. Without this method of saving genetic mutations, a species would have to hope that it would encounter a beneficial mutation sometime soon after the environmental change. The possibility of this is low and would take a significant amount of time in which the species might die off. The ability to suddenly express a vast amount of mutations would cause fast and drastic changes in organisms and be responsible for evolutionary change or divergence of species.
Jennifer Davis
41363007
Rutherford, L Suzanne and Lindquist, Susan. (1998) Hsp90 as a Capacitor for Morphological Evolution. Nature, Macmillan Publishers Ltd Vol. 396. (http://www.tulane.edu/~biochem/lecture/mcbp607/rutherford_lindquist.pdf)
Pigliucci, Massimo (2002) Buffer zone. Nature publishing group Vol. 417.
Jennifer Davis
41363007
Rutherford, L Suzanne and Lindquist, Susan. (1998) Hsp90 as a Capacitor for Morphological Evolution. Nature, Macmillan Publishers Ltd Vol. 396. (http://www.tulane.edu/~biochem/lecture/mcbp607/rutherford_lindquist.pdf)
Pigliucci, Massimo (2002) Buffer zone. Nature publishing group Vol. 417.
Heat shock proteins shock cancer researchers
Heat Shock Proteins or HSP’s are a group of protector proteins that have a large effect on the phynotypic expression of genes. It has been known for a while that a particular group of HSp’s (HSP70) have a marked effect on the growth and development of tumours.
There has been recent research studying the effect of other HSP’s in the HSp70 group on the morphology of cancerous cells and growths. In Genes and DEV. 2005, By implementing RNA interference and targeted knockdown of individual HSP’s from the HSP70 family, it was revealed that for cancer cell growth and development both HSP70 and HSP70-2 were essential. When cancer cells were deprived of either HSP70 or HSP70-2 there was a radical change in morphology, the depletion of HSP70-2 also induced the expression of cytokenine-1 which is a target of a tumour suppressing protein.
HSP70 inhibits cell death induced by a number of varying stimuli, it is this property promotes tumourogenisis. In fact HSP70 occurs in high abundance in a variety of malignant tumours. By using antsense, oligonucleatides or adenoviral transfer of antisense to deplete HSP70 cancer cells can be selectively killed not only in cell cultures but also in tumour xenografts in mice. With more research perhaps transposable to human cancer cases.
primary resorce
Heat shock proteins shock cancer researchers
Heat Shock Proteins or HSP’s are a group of protector proteins that have a large effect on the phynotypic expression of genes. It has been known for a while that a particular group of HSp’s (HSP70) have a marked effect on the growth and development of tumours.
There has been recent research studying the effect of other HSP’s in the HSp70 group on the morphology of cancerous cells and growths. In Genes and DEV. 2005, By implementing RNA interference and targeted knockdown of individual HSP’s from the HSP70 family, it was revealed that for cancer cell growth and development both HSP70 and HSP70-2 were essential. When cancer cells were deprived of either HSP70 or HSP70-2 there was a radical change in morphology, the depletion of HSP70-2 also induced the expression of cytokenine-1 which is a target of a tumour suppressing protein. HSP70 inhibits cell death induced by a number of varying stimuli, it is this property that promotes tumourogenisis. In fact HSP70 occurs in high abundance in a variety of malignant tumours. By using antsense, oligonucleatides or adenoviral transfer of antisense to deplete HSP70 cancer cells can be selectively killed not only in cell cultures but also in tumour xenografts in mice.
There has been recent research studying the effect of other HSP’s in the HSp70 group on the morphology of cancerous cells and growths. In Genes and DEV. 2005, By implementing RNA interference and targeted knockdown of individual HSP’s from the HSP70 family, it was revealed that for cancer cell growth and development both HSP70 and HSP70-2 were essential. When cancer cells were deprived of either HSP70 or HSP70-2 there was a radical change in morphology, the depletion of HSP70-2 also induced the expression of cytokenine-1 which is a target of a tumour suppressing protein. HSP70 inhibits cell death induced by a number of varying stimuli, it is this property that promotes tumourogenisis. In fact HSP70 occurs in high abundance in a variety of malignant tumours. By using antsense, oligonucleatides or adenoviral transfer of antisense to deplete HSP70 cancer cells can be selectively killed not only in cell cultures but also in tumour xenografts in mice.
An Evolutionary Angle: “Jumping Genes” Generate Interest in Hsp Genes
An Evolutionary Angle: “Jumping Genes” Generate Interest in Hsp Genes
Translation of heat shock proteins (Hsp) is enhanced under heat stress due to factors like decondensed chromatin and nucleosomes found in the promoter. This exposure of the promoter in turn gives easy access to P elements. P elements are a specific class of TEs that are highly clustered in the promoters and can have either forward or reverse orientation.
There could an evolutionary link between Hsp being specifically targeted by the P elements and Hsp having evolved distinctively from the genome which makes them efficient at dealing with heat stress. Hsp help fold up proteins correctly and degrade denatured proteins but mutations get exposed under stress leading to selection. TEs are powerful mutagens that alter the genome enabling selection to act. Even though mutations are mostly deleterious, P element insertion can be advantageous for Drosophila. P element insertions in Hsp have mostly resulted in decreased gene expression. This helps prevent Hsp accumulation, which can be harmful when not under heat stress, leading to positive selection for P element insertions.
Only in the last century have P elements been found in the Drosophila genome. This could be attributed to the mutation studies being done which have caused such rapid evolution. Since the generation time is very short for Drosophila, evolution can be accelerated and future generations can be tested and compared with the present.
Primary reference:
Walser, J., Chen, B., Feder, M.E., 2006, “Heat-Shock Promoters: Targets for Evolution by P Transposable Elements in Drosophila” PLoS Genetics, Vol.2, No. 10, pp. 1541-1554 Web Address: http://genetics.plosjournals.org/perlserv?request=get-document&doi=10.1371/journal.pgen.0020165
Written by: Vinisha Kapadia (41061554)
Translation of heat shock proteins (Hsp) is enhanced under heat stress due to factors like decondensed chromatin and nucleosomes found in the promoter. This exposure of the promoter in turn gives easy access to P elements. P elements are a specific class of TEs that are highly clustered in the promoters and can have either forward or reverse orientation.
There could an evolutionary link between Hsp being specifically targeted by the P elements and Hsp having evolved distinctively from the genome which makes them efficient at dealing with heat stress. Hsp help fold up proteins correctly and degrade denatured proteins but mutations get exposed under stress leading to selection. TEs are powerful mutagens that alter the genome enabling selection to act. Even though mutations are mostly deleterious, P element insertion can be advantageous for Drosophila. P element insertions in Hsp have mostly resulted in decreased gene expression. This helps prevent Hsp accumulation, which can be harmful when not under heat stress, leading to positive selection for P element insertions.
Only in the last century have P elements been found in the Drosophila genome. This could be attributed to the mutation studies being done which have caused such rapid evolution. Since the generation time is very short for Drosophila, evolution can be accelerated and future generations can be tested and compared with the present.
Primary reference:
Walser, J., Chen, B., Feder, M.E., 2006, “Heat-Shock Promoters: Targets for Evolution by P Transposable Elements in Drosophila” PLoS Genetics, Vol.2, No. 10, pp. 1541-1554 Web Address: http://genetics.plosjournals.org/perlserv?request=get-document&doi=10.1371/journal.pgen.0020165
Written by: Vinisha Kapadia (41061554)
Putting the retro (transposons) into epigenetics.
The question whether environment and DNA effect phenotype and behaviour of an organism are being countered by another exciting area of research: epigenetics. This challenging area suggests an organisms emotional and physical fitness may be linked to its environment and the past conditions its parents were exposed to.
A paper called “Stress and transposable elements: co-evolution or useful parasites?” by Pierre Capy et al (2000) reported that transposable elements may respond to different external environmental signals and effect the hosts fitness to varying degrees. These effects may create more genetic variability for selection to choose from and improve the populations ability to withstand environmental change over time.
Parallels may be made to another journal article “Epigenetic variation and inheritance in mammals” by Vardhman Rakyan & Stephen Beck (2006). The article described how retrotransposons effected the expression of the agouti viable yellow allele in relation to coat colour and diabetes in mice. After exposure to a certain controlled environment, an unmethylated retrotransposon integrated upstream of the agouti gene and promoted expression of a yellow coat and a tendency to develop diabetes. However, another set of conditions caused methylation of the retrotransposon and it promoted expression of the wild type phenotype and normal health in the mouse.
Transposable elements by their design alone are quite radical and exciting. The fact they are being associated with the environment, parental effects and an organisms fitness, highlights their significance to future biomedical research.
Student: Gabrielle Ahern
Nr: 30010855
Primary Source:
Capy, P. et al (2000) “Stress and transposable elements: co-evolution or useful parasites?” Heredity 85: 101- 106
Secondary Source:
Rakyan V.K. & Beck, S. (2006) “Epigenetic variation and inheritance in mammals” Current Opinion in Genetics & Development 16: 573-577
Further sources of information:
Morgan, H.D. Sutherland, H.G. Martin, D.I. Whitelaw, E. (1999) “Epigenetic Inheritance at the agouti locus in the mouse.” Nature Genetics 23: 314 - 318
Websites:
Oxford English Dictionary Online
http://dictionary.oed.com.ezproxy.library.uq.edu.au/
09 October 2007
Does your mother’s nutrition influence your susceptibility to disease in later life?
Diseases you may contract throughout your life might be influenced by the diet of your mother while she was pregnant or what you were feed as a baby. It has been long known that genes and the environment influence an organism’s phenotype (appearance). Therefore, causes of disease would be assumed to be genetically or environmentally based. However, a recent study has shown that adult diseases are potentially linked to metastable epialleles, which are types of epigenetic factors. Epialleles are mechanisms of inheritance other than DNA, that have been shown to modify certain characteristics of an individual, passing this on information to offspring. Epialleles are highly influenced by environmental factors, especially those that occur in early embryonic development. Such changes in structure of non-DNA regions at early development, called metastable epialleles, can cause a ‘cascade effect’, where the epialleles spread throughout the body as a result of mitosis. These modifications ultimately alter the expected phenotype, affecting an individual throughout its life. If metastable epialleles lead to a detrimental phenotype, results could be devastating. For example, diets low in folic acid, vitamin B12, choline and betaine affect an epiallele in mice which induces obesity and tumorigenesis. Epialleles that occur in the human epigenome may also have detrimental outcomes. This illustrates the importance of research into how the environment, such as embryonic and post-natal nutrition, affects metastable epialleles, which in turn alters phenotypic characteristics, possibly leading to disease.
References
Dolinoy, D.C., Das, R., Weidman, J.R. and Jirtle, R.L. (2007) Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases, Pediatric Research, 61:30R-37R.
Rakayan, V.K. and Beck, S. (2006) Epigenetic variation and inheritance in mammals, Current Opinion in Genetics and Development, 16:573-577.
Jessica Walsh
40996800
References
Dolinoy, D.C., Das, R., Weidman, J.R. and Jirtle, R.L. (2007) Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases, Pediatric Research, 61:30R-37R.
Rakayan, V.K. and Beck, S. (2006) Epigenetic variation and inheritance in mammals, Current Opinion in Genetics and Development, 16:573-577.
Jessica Walsh
40996800
IsfA - Stopping Evolution At Its Source
Antibiotic resistance has long been the bane of the medical profession. As strains of bacteria become exposed to various antibiotics some are able to survive due to random genetic variability in the population. These members of the population have a mutation in their genome that confers antibiotic resistance, allowing them to reproduce and spread until a new resistant strain of organism emerges. A recent study by Cirz et al. (2005) (as cited in Gene, M. 2005) showed that bacteria actively induce these mutations to increase variability when under stress through a process known as the SOS response.
However the answer to this problem may already exist. In 1999, a paper by Felczak et al. showed that there was a mutation in E. coli which inhibited SOS induced mutagenesis. Scientists tested the antimutagenic effects of the isfA mutation on a variety of mutator strains in the Lac Z gene. An analysis revealed that the isfA mutation inhibited UV induced transitions and transversions (known to use the SOS pathway) but had no effect on mutagens that did not involve the SOS pathway(Felczak et al., 1999). The isfA mutations acts to inhibit the processing of UmuD to UmuD'; an essential process in SOS mutagenesis resulting from Lex A cleavage.
In closing, SOS mediated directed evolution in bacteria is a problem with no current solution other than the introduction of new antibiotics. However, this is just a stall at best. The isfA mutation may be able to increase the lifespan of many antibiotics by disabling the very mechanism by which bacteria become resistant. Further research is required before this mutation can be applied to medical fields, however it has lots of potential.
Tom Reddel
41202656
Primary reference
Felczak, M., Bebenek, A., Pietrzykowska, I. (1999), The isfA mutation specifically inhibits SOS-dependent mutagenic pathway and does not selectively affect any particular base substitution. Mutagenesis. 3(14), pp 295-300
http://mutage.oxfordjournals.org/cgi/content/full/14/3/295#T2
Secondary references
Cirz, R., Chin, J., Andes, D., Crecy-Lagard, V., Craig, W., Romesberg, F. (2005), Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biol 3(6) pp 176-186
biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030176&ct=1
Gene M, (2005), Evolution Under Intrinsic Control
http://www.idthink.net/biot/lexA/index.html
However the answer to this problem may already exist. In 1999, a paper by Felczak et al. showed that there was a mutation in E. coli which inhibited SOS induced mutagenesis. Scientists tested the antimutagenic effects of the isfA mutation on a variety of mutator strains in the Lac Z gene. An analysis revealed that the isfA mutation inhibited UV induced transitions and transversions (known to use the SOS pathway) but had no effect on mutagens that did not involve the SOS pathway(Felczak et al., 1999). The isfA mutations acts to inhibit the processing of UmuD to UmuD'; an essential process in SOS mutagenesis resulting from Lex A cleavage.
In closing, SOS mediated directed evolution in bacteria is a problem with no current solution other than the introduction of new antibiotics. However, this is just a stall at best. The isfA mutation may be able to increase the lifespan of many antibiotics by disabling the very mechanism by which bacteria become resistant. Further research is required before this mutation can be applied to medical fields, however it has lots of potential.
Tom Reddel
41202656
Primary reference
Felczak, M., Bebenek, A., Pietrzykowska, I. (1999), The isfA mutation specifically inhibits SOS-dependent mutagenic pathway and does not selectively affect any particular base substitution. Mutagenesis. 3(14), pp 295-300
http://mutage.oxfordjournals.org/cgi/content/full/14/3/295#T2
Secondary references
Cirz, R., Chin, J., Andes, D., Crecy-Lagard, V., Craig, W., Romesberg, F. (2005), Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biol 3(6) pp 176-186
biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030176&ct=1
Gene M, (2005), Evolution Under Intrinsic Control
http://www.idthink.net/biot/lexA/index.html
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