josh, sam, & kevin: following a rosetta@home study

What we've accomplished

2009-05-03T19:15:00.000-07:00

Computing and credit
Total credit
6,528
Recent average credit
5.11

2009-04-23T16:33:00.000-07:00

Malaria Questions

1. What is the estimate h^2? The broad-sense heritability for sickle cell anemia is low, but the narrow-sense heritability for sickle cell anemia is high.

2. How much does selection act on this Trait? In general, selection would strengthen the heritability and reproduction of this trait, mainly because due to reproductive success causes malaria/sickle-cell anemia to persist and adapt within a population. For example, if the virus mutates, it will respond in regards to selection in which what occurs on one loci affects the frequency of alleles occurring on the second locus, making it occur more frequently in the population. Since the narrow-sense heritability is high, then this eliminates the contribution of dominance within its genetic variation.

3. What effect would inbreeding have on this trait? Since Malaria, or sickle cell anemia rather, is an autosomal recessive trait we would expect inbreeding to increase the number of people with "full blown" sickle cell anemia. Inbreeding usually tends to bring out autosomal recessive diseases.

Group Questions

2009-03-26T17:03:00.000-07:00

1. According to another PNAS paper (“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?

When reflecting on this geographically, I imagine that one researching this would typically find the disease alleles to be common in locations where those who have been more affected by systemic lupus and those who are immuno compromised individuals (in which the disease systemic lupus effects the immune system) in locations such as Africa where there is also high statistics of the threat of malaria. These disease alleles would statistically reduce the cases of malaria. Regarding sickle cell anemia and whom it primarily affects those of African descent, the immunity is conferred hypothetically because the paper discusses how the virus is evolving and is correlated to other diseases that are in the geographic location.

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

It’s important to study malaria because in this specific study, we are shown how the virulent strains that do not kill their intermediate host have a greater chance at increasing its genetic variation and thus cause change in an evolutionary sense. We can study its implications on mice because we can use things such as PCR and other advanced biotechnology techniques in order to discover new things about the virus in a controlled environment.

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

Darwin's postulates:
Variation exists among individuals of the same species - Plasmodium reproduces mitotically within hosts; variation is minimal. On a large scale, however, much variation exists between strains of Plasmodium.
At least some variations are hereditary - In order to outlive hosts, Plasmodium must infiltrate the bloodstream adequatley for mosquitoes to ingest gametocytes.
In every generation, more offspring are produced than can survive - Only gametocytes that are ingested by mosquitoes survive.
Natural selection operates on populations - Plasmodium strains that are the most virulent without killing their respective hosts are the most likely to pass on their genes. The longer that the host remains alive, the more opportunities there will be for mosquitoes to ingest and inject into future hosts.

4. On page 7624, the authors assert that “virulence is a consequence of a parasite’s efforts to maximize its fitness.” What is misleading about this sentence, and how could it be re-worded to accurately address how selection works?

The sentence is misleading because a parasite's fitness depends largely upon the host's ability to survive. An alternative sentence: "In order to maximize fitness, parasites must effectively balance virulence with their respective host's ability to survive."

5. If, as the authors suggest, more virulent strains have a competitive advantage within their mouse host, why do they conclude (page 7628) that “parasites evolve some intermediate level of virulence”?

It is said, “parasites evolve some intermediate level of virulence,” because virulence is a by-product of with-in host competition, but extreme virulence will kill the host to quickly and prevent transmission. Parasites evolve virulence at an intermediate level in order to beat out other parasites and become transmitted while not killing their host too promptly.

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

It is important to study protein folding/misfolfing in malaria even though we know its cause, because if we under stand how the protein interacts we can then formulate more potent vaccines/immunizations.

Ask the Expert

2009-03-03T20:07:00.000-08:00

On Tuesday, March 3rd, 2009, we interviewed Dr. Mary Haskins at Rockhurst University about malaria.

Here are a few highlights from the interview:

1. Besides being a Professor of Biology at Rockhurst University, what is your experience with malaria?

I’ve travelled through 2 countries (Dominican Republic and Botswana, Africa) in
which malaria is a problem. I took medication for malaria on both trips. The 2nd
time, I received meds that have the side effect of “bad dreams." Fortunately, I
did not experience the bad dreams. However, I know individuals that have, and
the dreams are really “nightmarish”…far worse than your “typical” bad dream.

2. When was malaria first discovered?

1880 was the first formal identification – however, it’s recorded in the ancient
Chinese history. Based on the symptoms, the first records date back to about
2700 B.C.

3. What evidence is there that malaria existed back then?

One large source of evidence is the fact that they documented the use of
mosquito nets to prevent illnesses. Although people back then may not have
understood the complexity of life, they did posses a great deal of knowledge
about how to stay healthy.

4. What are the symptoms of malaria?

Predictable cycles of chills and fever are the most characteristic and
identifiable. Generally flu-like symptoms until the “cycle” starts…so it may
initially go untreated.

5. What other types of organisms contract malaria?

Other mammals and some reptiles.

6. The vector of malaria is the mosquito. However, may all mosquitoes contract malaria?

No, only female mosquitoes…because they are the ones who take a blood meal. Not
all genera carry the protist vector (Anopheles mosquitoes carry it).

7. The idea behind the rosetta@homes grid-computing project is to make mosquitoes resistant to Plasmodium by eliminating genes required in the mosquito for the parasite to live. Our part of the project is to use our computer based design methods (ROSETTA) to engineer new enzymes that will specifically target and inactivate these genes. Do you believe this is possible/worthwhile? Do you foresee any problems, based on what you know about malaria?

First, you would need to determine what genes in the mosquito are required for
the parasite to survive. If those genes are vital for mosquito survival then
changing those genes would also wipe out the mosquito population which may
result in producing additional problems. (I know a world without mosquitoes
might SEEM attractive…but the mosquitoes are a link in the food web. Therefore,
eradicating them may produce problems you haven’t yet thought of) .

Both
mosquitoes and Plasmodium may mutate to avoid the problem you intend to
pose for them, thus rendering your treatment method ineffective. The rapid rate
of mutation is why antibiotic resistance has developed so quickly

It’s a
nice idea, but nature is never as “simple” as you think. Therefore, I think this
method will prove to be more challenging than it seems. In addition, whatever
genetic changes you produce in the mosquitoes would have to be heritable or it
would be a waste of money.

8. Approximately how many people have the infection worldwide? On which continent is malaria most prevalent?

Africa is hardest hit, and about 40% of the world population is at risk. Of
those people, about 500 million succumb to the disease each year, and about 1
million people die each year. About 1,500 people in the US come down with
malaria annually…usually after a trip abroad.

9. Do you follow scientific technology or find it personally useful as a professor to learn more about science? Does it make it all the more interesting to you to see how it helps research develop?

Yes and yes – Trichomonas cruzi has been found to change the DNA of its
host. Therefore, the infected organism naturally reproduces it, and it may be
passed on in meiosis. Such discoveries lead us to question how much DNA is
actually the result of our ancestors?

A Jesuit priest is believed to
have “discovered” quinine and that was the first treatment for malaria.

Drug-Resistant Malaria Parasites

2009-02-15T20:34:00.000-08:00

"Since the wide-scale deployment of antimalarial drugs in the latter half of the 20th century, human malaria parasites have been under tremendous selection pressure to evolve mechanisms of resistance" (White, 2003).

In other words, because the malaria parasite, Plasmodium, has been exposed to inadequate dosages of antimarial medications, it has grown resistant to many of the medicines that we have today.

Mosquitoes are the vector for malaria parasites and they use an anterior mode of transmission (the virus is transmitted through the bite of a mosquito and not its feces).

To better understand how humans are able to contract malaria, this diagram shows the life-cycle of Plasmodium.

Picture acquired from:

http://www.dpd.cdc.gov/dpdx/HTML/ImageLibrary/Malaria_il.htm

Our participation in Rosetta@home helps to fight diseases like malaria by generating new designs for protein folding. Proteins are extremely complex molecules; at a molecular level, form=function.

Before we forget, we've got to make a shout out to baddest man in the biological universe: C. Dar. Happy 200th fresh. R.I.P. big boy. U'll remain in our hearts 4eva.

References:

White, N.J., Pongtavornpinyo, W. 2003. "The de novo Selection of Drug-Resistant Malaria Parasites."

Biological Sciences. Vol. 270, No. 1514

BOINC platform

2009-02-03T16:50:00.000-08:00

http://boinc.bakerlab.org/

evolution class & rosetta@home.

2009-02-03T16:38:00.001-08:00

This weblog consists of a group (Sam, Kevin, and Josh) doing a study of the Rosetta@home research project. We are a group from Dr. Mindy Walker's Evolution class at Rockhurst University. Josh is running a grid-computing program for the topic and we will essentially be adding new material to this weblog as we go into more research throughout the semester.