Grid Computing Project

Project summary:
Our grid was Rosetta@home. Often times our computer was sent different tasks, but they were all involved with protein folding. Currently our computer started a RosetteMini task that is 4% done and is expected to finish on May 10th. For Rosetta@home our computer has contribute 84.6 units, averaging 1.17 units per day. According to the statistics for our grid each unit/result takes approximately 5 hours. On Monday there were 115, 706 results returned. The Go Fight Against Malaria project urges scientists to work together rather than to compete in finding a cure for Malaria. Just while finishing this blog post the current project is now 17% complete. Our average units contributed has risen in the past couple of weeks according the statistics graph.

Questions – Malaria

Questions 2-6 are based on the Philosophical Transactions of the Royal Society of London article entitled “Virulence in Malaria: an Evolutionary Viewpoint” by MacKinnon and Read (2004).

1. According to another paper (PNAS “Systemic lupus erythematosus-associated defects in the inhibitory receptor FcyRIIb reduce susceptibility to malaria” by Clatworthy et al. 2007), systemic lupus confers some immunity to malaria.  Geographically, where would you expect the disease alleles to be common, and why?  Considering what you know about sickle cell anemia, how do you hypothesize that this immunity is conferred?

 

Response: Geographically, we would expect the disease alleles for systemic lupus to be somewhat common in areas where malaria is prevalent.  Possessing these disease alleles would statistically reduce the threat of malaria.  Furthermore, knowing what we know about sickle cell anemia and its heterozygote advantage, we hypothesize that individuals heterozygous for systemic lupus are selected for.  One allele protects against malaria and the other protects against systemic lupus.

 

2. In an evolutionary sense, why is it informative to study malaria and its implications in mice?

Response: Mice are the classic vertebrate model organism and are used in many studies. Mice and humans share orthologous genes and homologous proteins which is why they make a good model for humans. Because of this, it is easier to see the effects of malaria in a lab rather than a field study. It is also convenient to study immune versus naive hosts. Mice are easier to study because death can be documented and it is not an ethical issue, like studying the death rate or infection rate in humans. Since mice are the classic vertebrate model, malaria and its implications will be similar to those in humans.

 

3. Apply Darwin’s four postulates to within-host Plasmodium virulence and transmission success.

 

Response: a. There is variation in Plasmodium virulence and transmission success.

b. Some of this variation is heritable, namely the high multiplication ability and transmission-related advantages.

c. More Plasmodium are produced than can survive. Some are killed in host death for example, while some may be killed by reduced infectivity of mosquitoes.

d. The Plasmodium with higher multiplication ability and other transmission-related advantages survive and reproduce in the host, and thereby pass on their genes in subsequent generations which infect other hosts. 

4. On page 973, the authors assert that “drug resistance becomes a problem within 5-30 years of first using a drug” and that this “is indicative of their potential to evolve rapidly.”  What does this tell you about the efficacy of vaccines?  Why should your Tropical Medicine physician know about evolution?

Response:Vaccines are able to produce a result for a while, but the parasite evolves quicker than new medicines are being produced. And on that note new vaccines can not be produced unless the virus has evolved to resist the the old one, and the devolopers of the vaccine are able to figure out how the parasite has changed and is able to resist the vaccine. They need this information to make the new vaccine effective. The vaccine will work for a while then the infection rate will rise again once the parasite has evolved to resist the vaccine, becoming a cycle. This is not uncommon in medicine, as we see this with bacteria and antibiotics. Your Tropical Medicine physician should know that there are different parasites in different geographical areas. The physician should also know that in some geographical areas parasites evolve differently than in others, and become resistant to vaccines. You and your physisican should research where you plan to travel and find out which parasites are virulent in that area and treat accordingly.

5. If, as the authors suggest, more virulent strains have a competitive advantage within their mouse host, why do they conclude that “parasites evolve some intermediate level of virulence”?  What mode of selection on this quantitative trait does this exemplify?

Response: Even though more virulent strains have a competitive advantage within their mouse host, parasites must evolve an intermediate level of virulence because a high level of virulence would kill the host too quickly and result in a lack of transmission to other hosts.  This is a great example of a stabilizing selection in which the intermediate phenotype is favored and the extremes are weeded out.

6. Why is it important to study protein folding/misfolding in malaria, even though we know its cause?

Response: It is necessary to study protein folding/misfolding in malaria because one of the virulence factors of the malaria parasite uses antigenic variation on the surface of red blood cells in order to hide from the host. In this way, the parasite can avoid destruction by the immune system. The surface antigens which have been altered by the malaria parasites are proteins. By studying the structure of these proteins, we may gain key insights in to effective treatments of malaria by targeting the parasite through a different mechanism.