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.
Subscribe to:
Posts (Atom)