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.

"Virulence in Malaria: an Evolutionary Viewpoint"

Below is a link to a scientific article pertaining to both evolution and malaria:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693375/pdf/15306410.pdf

The Interview!

Interview on Malaria

We chose to interview Dr. Mary Haskins, a professor of biology at Rockhurst University.  Her expertise in malaria stems from her personal visits to countries in which malaria is prevalent, as well as the extensive amount of research she has done on the subject.  Thank you, Dr. Haskins!



How did you get into studying malaria?

Well, I teach a course in parasites, and I think parasites are very fascinating.  Also, malaria is one of the major parasitic issues affecting our world today.  I’ve also been to several countries where malaria is an issue and I have been on malaria meds four times in my life.  So, having gone to countries where malaria is an issue, I wanted to be educated about the risks and prevention techniques.

Why should a doctor/researcher studying malaria know about evolution?

One of the biggest problems with malaria, as with other diseases, is that once you develop a drug to treat the organism that is the problem, then you select against all of those that were weak.  Those that were not selected against survive, so over time you end up with a population of organisms that are not going to be susceptible to that drug treatment.  So you need to understand evolution to appreciate the evolutionary process that your organisms are undergoing and understand why drugs that work at time “A” may not work at another point in time.  Organisms can adapt and evolve resistance

We read about HIV, in which they often use a cocktail of drugs in an attempt to fight the disease.  Is the same thing done for malaria?

To my knowledge, they do not use a drug cocktail with malaria.  They use a specific drug, and there are several different drugs on the market.  Depending on where you go, you might take drug A or drug B.  If you go to one country you might take drug B, because the parasites in that country are resistant to the drugs used in another country.  So you have to know which form of plasmodium you are dealing with because there are different species, and you have to know which ones are resistant to which drugs.  There is a lot of background research that needs to be done by tourists, as well as the physicians that advise those tourists.

For our evolution project we are doing grid-computing that looks at protein folding.  How does finding certain ways that a protein folds help find a cure for malaria?

I would assume that if you could look at protein folding and maybe find a way in which you could interfere with the process, then that would be a useful mode of action for a pharmaceutical drug. 

Do you think it is possible for there to be a cure for malaria since it seems to mutate, or evolve, so much?

I don’t know.  There are a lot of reservoir hosts, which are animals where the parasite can “hang out”.  You could theoretically get rid of it from the human population, but if a mosquito were to then go bite a reservoir host, the disease could find its way right back into the human population.  There is a ton of money being dumped into medically combating this disease, and major foundations (including the Gates Foundation) have a goal of eradicating malaria.  Whether or not that will happen in the near future, that is anyone’s guess.

Do you think it is plausible to eradicate malaria by just putting money into the medical treatment of the disease?  Or do you think it would be better to improve the social environment (e.g. living conditions)?

I think we need a multipronged approach.  We have to have pure education in regards to how malaria is transmitted, how it can be prevented, and drug treatments.  I think one approach would be wrong.  You have to attack it from a broad spectrum to have a higher chance of success.  And there are some examples of things that have been wiped out, so it’s not unheard of, but when you think about all the reservoir hosts it seems like quite the challenge.

What are some common misconceptions about malaria that you encounter?

A lot of people do not understand where malaria actually comes from.  They know it’s associated with mosquitoes, but they don’t know that it’s a protozoan carried by mosquitoes.  Also, I think some people believe that if you get it you just go to the doctor and you’re cured, and that is not necessarily true.  Two of the four species (of malaria) may be capable of residing within an individual for their entire life.  The parasite can go into remission and you may not show any symptoms but, at some point in time, it will come out of remission and you will experience those symptoms.    

Can you give us an example of how the malaria parasite is treated?

Malaria is one of the easier parasites to treat in the sense that there is actually a treatment that has very minor side effects.  Basically, before you go to a country with malaria, while you are there, and a few weeks after you get back, you take oral tablets as a preventive measure.  The length of time you take the pill depends on the country and relative species of plasmodium, as well as which drug you are taking.  The pill that you are taking would have the chemical in it that is going to destroy the parasite, but there is some evidence that for at least 2 species the parasite can hide out in the liver.  As a result, the drugs cannot get to them and treat them effectively, leaving the door open for recurrent episodes. 

Have you had first-hand contact with malaria patients?

Not to my knowledge.  I have never been in an area where I felt like I was at risk.  A lot of communities spray their towns with chemicals that kill off the mosquitoes.  That breaks the transmission to people, but now you have all of these harmful chemicals in the air that you are breathing in.  Now, this isn’t just done in non-industrialized countries.  This has been done in the United States.  When I went to Belize last year I did not see a mosquito the whole time I was there, and I believe it was because they sprayed so much that they essentially knocked out the population.  Now what that means is if you ever got a malaria-carrying mosquito that evolved to be resistant to those chemicals, you just made it harder to knock that population, and disease, out. 

Are mosquitoes the only way malaria can be transmitted to humans?

Yes, they are the only vector.  And it is only the female mosquitoes.

Do malaria treatment drugs have side effects?

Yes, but I don’t remember the long list.  One of the drugs (mefloquine) I have been on, however, has the side effect of causing horrendous, HORRENDOUS nightmares.  Unfortunately, they do not tell you that side effect when they give you the drug.  It’s not a pleasant experience when you are in a new country, unfamiliar territory, possibly by yourself, and you go to bed and wake up in the middle of the night because of a traumatizing nightmare.  Now, this is only a supposed side effect.  I personally have never had this experience, but a former student of mine had a sister who went on a service trip (and was taking mefloquine) and experienced traumatizing nightmares almost every night she was there.

Does Rockhurst require you to be on anti-malarial drugs when you go on service trips?

No.  Basically, Rockhurst tells you to go to your physician and ask them what you should do.  Some physicians are good about getting you the right information and some physicians are not.  I had a young lady last year whose doctor told her that Belize did not have malaria.  That’s not true.  You can go to the CDC website and see that there are three districts in Belize which have cases of malaria.  Now, the odds of you getting it are still slim, but I think you should be allowed to make the educated choice: either choosing not to take the drugs because the risk is low or choosing to take them no matter what.  My guess is the doctor probably assumed that she was going to Belize City, which is in the northern part of the country and is a more touristy area (malaria is more prevalent in the southern part of the country, where we were going), thus advising her not to worry about it. 

In which country is malaria most prevalent?

It would be an African country, though I wouldn’t be able to pick out which one.  Interestingly, when I went to Cameroon and then came back to the U.S. and went to the Red Cross to donate blood, Cameroon was not listed under the “cannot donate” list for recent visitors.  This is odd because malaria is, in fact, present in Cameroon.  They did have Belize listed though.  That may have to do with the type of malaria present within each respective country, but I cannot say for sure.



Reflection

Our interview with Dr. Haskins was extremely informational. The interview gave us a lot of insight into the "real" part of our Evolution project, not simply the grid-computing/computer aspect. Dr. Haskins provided us with first hand knowledge on the topic of malaria which was very informative.  We covered many aspects of the topic and learned new and interesting things. It was beneficial for our group to listen to an expert speak regarding the topic of malaria and it was interesting to hear her personal views regarding the disease and potential for a cure.

Introduction

The purpose of this blog is to follow the progress of the grid computing project Rosetta@home, which is dedicated to the search for protein structures that could serve as potential treatment for several diseases, one of those being malaria. The participation in a grid computing network is part of the service-learning requirement for our spring 2013 Evolution class.

Included here is an excerpt from the website HowStuffWorks.com for general information about malaria:
     "Suppose you're on a summer vacation in Southern Florida watching the sun set, and the mosquitoes are buzzing. You may suffer a few bites and be uncomfortable with the itchy welts. But if you're a mother in tropical Africa, a biting mosquito is one of your worst fears, because it can transmit malaria. In this article, we'll learn about this serious, often fatal disease and find out why it's one of the world's most pressing public health concerns.

Malaria is an infection transmitted by a certain type of mosquito. Eradicated in the United States and other developed countries, it is now a disease of tropical areas in Africa, Asia, Central and South America, the Middle East and Oceania. Today, malaria is widespread in more than 100 countries, affecting about 300 million people and causing 1 million deaths a year. More than 90 percent of cases occur in tropical Africa, with young children and pregnant women making up most cases. In Africa, malaria is the leading cause of death for children under the age of five.

Globally, more than 2 billion people are at risk for malaria, with the majority of cases occurring among the poorest 20 percent of the world's population. In these poor and often rural areas, healthcare systems are inadequate and sanitation is poor. Increasing resistance to the drugs used to treat malaria and insecticides used to prevent it also contribute to the growing prevalence of the disease and to its resurgence in areas where it had been eliminated."
 source: http://health.howstuffworks.com/diseases-conditions/infectious/malaria.htm

To read about symptoms and prevention of malaria, see the following link: http://health.howstuffworks.com/diseases-conditions/infectious/malaria1.htm

Below is the link to the video created by the Rosetta@home organization.
http://www.youtube.com/watch?feature=player_embedded&v=GzATbET3g54#!

Below is a video detailing the life cycle of the malaria parasite within a human.
http://www.youtube.com/watch?v=szlfndj0TFE  (simplified video: http://www.youtube.com/watch?v=A2-XTlHBf_4)

Pictures pertaining to malaria from the National Geographic website (picture captions were also obtained from the National Geographic website):

"Her abdomen full of blood that will nourish her eggs, a female Anophelesmosquito takes to the air. Her next landing may be a dangerous one—for the human who receives her bite. The female Anopheles mosquito is the only insect capable of carrying the human malaria parasite."

"The invasion has begun. Microscopic magnification shows Plasmodium falciparum—the most virulent of the four malaria parasites that infect humans—destroying red blood cells in the liver. It digests a cell's hemoglobin, multiplies inside to the point of rupturing the cell, and rapidly spreads a new generation of infection."

"Washed garments hung to dry add splashes of color to weatherworn huts lining a river in Siem Reap, Cambodia. Poverty and weather conditions compound the problem of malaria. Outside of Africa, the majority of recorded cases of malaria are concentrated here and in eight other countries in Asia and South America."

"A sample of blood seems to captivate young locals at a malaria testing center in Iquitos, Peru. The first widely known remedy—from the bark of the cinchona tree—was discovered in the region in the early 1600s. The medicine, which became known as quinine, was so promising that malaria-ravaged Europe mounted expeditions to acquire the plant. Today, scientists search for more ways to fight the disease—including the development of a vaccine—as the parasite becomes resistant to the most common course of drugs."

"Caught in a wrenching cycle of shivering cold, high fevers, and profuse sweats, ecologist Michael Fay struggles through yet another attack of malaria at the Bomassa camp in Congo. Taking regular doses of antimalarial drugs can have long-term side effects, such as hearing loss and liver and kidney damage. So Fay, who has worked in Africa for decades, tends to wait until he feels achy and queasy before medicating himself. It's a risky approach that has twice come close to killing him."

"Contained panic shrouds the face of a mother whose child is suffering from malaria in Niger. Younger children are at higher risk of dying; their bodies have not developed enough immunity to fight the disease, which can infect their brains and kill them. Each day malaria claims the lives of about 3,000 children in Africa—one every 30 seconds. Researchers predict that in 2007, malaria will strike up to a half billion people worldwide. About a million—most under five years old and living in Africa—will die."