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)
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