Results

Our statistics for the three projects:

Total Run Time (y:d:h:m:s) (Rank)	5 days 13 hours 02 minutes 05 seconds
Points Generated (Rank)	15,596
Results Returned (Rank)	20

Human Proteome Folding - Phase 2

6,195 points

8 results generated

 Our total ranking is: 409, 955

We spent about six and a half hours generating each result.

Answers to Professor Walkers Questions

Questions – Influenza

Questions 1-6 are based on the Wildlife Research article entitled “Sialic acid profiles in the respiratory tracts of selected species of raptors: evidence for potential binding sites for human and avian influenza A viruses” by Han et. al (2011).

1. When the “bird flu” broke out in the early 2000s, it was referred to as H1N1.  In a molecular context, what does this mean?

      The Influenza A viruses are classfied according to the presence of two kinds of glycoprotein antigens found on the viral capsid: Hemagglutin (HA) and Neuraminidase (NA) (McGraw-Hill, 2007) . These two antigens are critical to the variability of new strains and host immunity. This nomenclature describes the order in which each varient was found. To this date, sixteen variances of the Hemagglutin antigen (H1-H16) and nine, Neuraminidase (N1-N9) have been identified. The HA antigen comprises almost 25% of the virus’ protein and is therefore, the main target of the antibodies produced in response to infection. Because it is so large, it is also the cause of variability in the evolution of new strains. It derives its name from the agglutination reaction that it produces with erythrocytes. The NA antigen makes up about 5% of viral protein and functions as an enzyme to remove sialic acid and aids the virus in release from the infected cell. It is therefore directly related to the infectious ability of the viral strain.

2. In an evolutionary sense, why is it informative to study human influenza and its implications in birds (or horses or pigs, etc)?

      Because influenza viral strains mutate so rapidly and can infect a variety of hosts, the infectious, evolutionary path a strain takes can be an interesting one. Avian species serve as the natural reservoirs for all identified Influenza A HA and NA strains (Han et al., 2011), while hosts such as pigs are believed to be “mixing vessels” for influenza strains because they can be infected by both avian strains as well as mammal strains (Ma, Kahn, Richt, 2008). In a pig, strains that originate from different hosts can undergo genetic reassortment to produce a new, possibly more virulent strain. So while avian strains may not directly infect humans, when such a strain first infects a pig, it may recombine so that it is able to then infect other mammalian hosts such as humans. According to Han et al. (2011), this host crossover can be ecologically and epidemiologically applicable as wild animal, domestic animal, and human species are increasingly forced to cohabitate in the same areas due to habitat encroachment.

3. Apply Darwin’s four postulates to within-host influenza anti-viral resistance.

            Charles Darwin had four postulates: 1) there is variation among individuals of the same species; 2) at least some of these variations are hereditary; 3) in every generation, there are more offspring produced than can survive; and 4) natural selection operates on populations.  The first postulate says there is variation among individuals and this can be seen in influenza because there is variation in the different strains of influenza along with the difference in sialic acid receptors seen in the birds.  In the second postulate, it says that at least some of these variations are hereditary, and this can apply to influenza because certain strains will continue to be passed from generation to generation.  In the study, it helps support this postulate because both avian and human influenza virus receptors were expressed in six different species of raptors. The third postulate states that in every generation there are more offspring produced than can survive.  This can be applied because there are some types of influenza that maybe produced that do not survive in a population.  An example of this would be the reisolation of the avian influenza virus in the pigeon population.  The last postulate is Natural Selection operates on populations.  This can be applied to influenza because in certain species different types of influenza will not be an affect on the given population.

4. On page 650, the authors assert that “No correlation between phylogeny of birds and their sialic acid receptor distributions was observed.”  Why wouldn’t a phylogeny of this character reflect the phylogeny of the group?  If the authors added more characters to their dataset, would it be more likely to reflect the true species phylogeny?

      The evolutionary history of the raptors can be attributed to the selection for or against specific traits throughout the course of the species’ history. Phylogenetic trees that illustrate this evolutionary history were based historically upon morphological traits, and only more recently on DNA genomics and molecular traits. However, the sialic acid receptors to which the Influenza A virus binds would not follow the phylogenetic history of raptor species for several reasons. These receptors are found within the epithelial lining of the respiratory tract of the raptors. It would be difficult to determine the type of sialic acid receptors found in ancestral species from fossil evidence, especially since such evidence is sparse, in variable conditions, and incomplete. Moreover, according to the article, the distribution of these receptors differs even within species (Han et al., 2011). As such, the sialic acid profile of an individual raptor could not be generalized to apply to an entire species. Other contributing factors than genetics, could contribute to the distribution of these receptors for each bird.

      If the researchers added more characters to determine phylogeny of the raptors, they would risk trading the more parsimonious phylogeny for one that is more complex. Phylogeny aims to determine the simplest explanation as it is considered the most correct.

            5. Explain why avian flu viruses are not directly transmissible from human to human.

            According to Han et al. (2011), a possible reason has to do with the type of receptors found in the human upper respiratory tract versus the lower respiratory tract and the type of receptor that the virus binds to in each host (p. 648). Avian strains usually bind to sialic acid receptors linked to galactose by a2, 3 linkages (SAa2,3-gal) while human strains usually bind to sialic acid with a2, 6 linkages (SAa2,6-gal).  The upper respiratory tract of humans mostly expresses the SAa2, 6-gal type of receptors which makes it unlikely that the SAaPLP2,3-gal preferring avian strains can bind to such receptors.

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

            In order for the influenza virus to enter into the cell it must first undergo protein folding.  Hemagglutinin is a viral protein in influenza that controls entry into the cell.  Hemagglutinin interacts with cell membrane in two specific ways.  One portion of hemagglutinin inserts into the membrane, refolds, and alters its structure which promotes viral entry.  Another portion of the hemagglutinin protein links the viral and cell membrane and refolds to bring the two together.  Therefore influenza is using protein folding in order to enter into the host’s cells and infect them. If the influenza virus is unable to perform this protein folding then it will not be able to infect the cells.  Thus, it is important to examine protein folding/misfolding in influenza because this can lead to possible new solutions for hindering the virus from infecting the host.

Sources:

Han et. al 2011 article:

            http://www.publish.csiro.au/paper/WR11003.htm

Ma, Khan, Richt 2008 article:

            http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702078/

      McGraw-Hill Microbiology:                              http://www.drugswell.com/winow/Medical%20Microbiology/Jawetz/39.htm

Protein Folding Sources:

            http://folding.stanford.edu/English/FAQ-Diseases

            http://folding.typepad.com/news/2012/02/update-from-the-kasson-lab-at-the-university-of-virginia.html

When it comes to Influenza there are many different studies. The article that we selected to look at is titled Sialic acid profiles in the respiratory tracts of selected species of raptors: evidence for potential binding sites for human and avian influenza A viruses. Please feel free to read about this by clicking on the link below.
 http://www.evergladeshub.com/lit/pdf11/Reed11wildlifeRes38-114-21-PythonTrapsFL.pdf

The Flu Interview

Honestly, who hasn't gotten the flu at one time or another in their life? You're miserable, fatigued, and you want to spend your afternoon lounging on the couch with a blanket on watching your favorite movie. When considering who we were going to interview for our grid computing project we really had to think about it. Everyone could technically be considered an expert having fallen to its peril at least once, but who would give us the best insight about Influenza and then it hit us...

Flashback to Fall semester of 2012: sitting in the back row in a sleepless stupor, only half listening to rambles about upcoming quizzes and tentative test dates. Oh, the joys of Microbiology at Rockhurst. Learning about bacteria and viruses that you'd never want to be infected by. It was then that Nicole and I (Katie) learned about Influenza together and its transforming properties that probably make it one of the most interesting viruses out there. So, in running with tradition, we chose to interview Dr. Janet Cooper. Dr. Cooper is a Professor of Biology at Rockhurst, who is well versed in all things Influenza, making her absolutely perfect to do the job! So without further adieu, our interview with Dr. Cooper:

                                                                                                                                                                                                                           

Why did you choose this field/career path?

I enjoy teaching, specifically Cell Biology. During my undergrad I avoided Comparative Vertebrate Anatomy (luckily!) and took Cell Biology instead. I was fascinated by the properties of water and how important it was to learn about concepts at a cellular level in order to understand the big concepts.

Obviously you have come in contact with hundreds of people who have contracted the flu, or have had it yourself, what is the importance of obtaining the flu vaccine?

Getting the flu vaccine is not only important for protecting you but also for protecting others who have some form of immunodeficiency. The idea of 'herd immunity' is very important when dealing with Influenza because it protects the people who are unable to receive the vaccine themselves due to immune compromised diseases like cancer.

Do you have any interesting stories about Influenza?

Actually I do. Recently, a  very close friend of mine contracted just a common form of the flu and due to him being immuno-compromised due to kidney dialysis, he was unable to receive the yearly flu shot. After a period of time he developed pneumonia and died shortly after. Unfortunately, it's situations like this where people do not realize the importance of getting a vaccine as a simple method to protect everyone around you.

Why should a doctor or researcher studying Influenza know about evolution?

 It's important that both doctors and researchers that are studying/treating Influenza know about evolution because they need to understand that change can and does occur. In the doctor's case, they need to know because they need to understand the best methods for treatment, like when and when not to use antibiotics. In the case of researchers, it is important to understand the importance of evolution in the study of Influenza in order to tailor and develop new medicines or vaccines to treat different strains. 

Does evolution play a role in the life of the Influenza virus?

Absolutely, you begin to see selection over time, once you get a vaccine developed for the current strains that are most likely to cause the worst symptoms, a new strain transforms. We never know if a more hazardous strain of Influenza will appear and there is always a possibility for a large epidemic that is difficult to treat due to recombination and mutations [In case you're a bit rusty the running definition evolution stands as the change of allele frequency over a period of time].

Is there anything unique about Influenza as compared to other viruses (infection cycle, etc)?

It contains eight different strands that are able to go through recombination and mutate. This is not necessarily unique to Influenza but what researchers are finding is that there are certain species, like birds, that serve as 'mixing vessels' for different Influenza viruses. Due to its ability to infect a vast amount of species, this can create a very unique strain of Influenza that may be difficult to treat.

Have you ever heard of/used grid commuting in your research?

I have never used it myself, but my brother is well versed in the topic! He was recently on the news as one of the discoverers of the largest known prime number. His group uses over one thousand computers to solve complex math problems. 

Fox 4 KC- Largest Prime Number Grid Computing

What do you think about using grid computing as a means of solving complex issues about Influenza?

 It may be important to use to help analyze a drug or vaccine. Grid computing would be very useful in testing to determine if an enzyme can fit at the cellular level to deactivate the virus. It could be used to solve many other things about Influenza as well.

Do you think resistance is a major issue in common society, not just with bacteria but also with viruses?

 Without a doubt, people look at antibiotics as the end all be all. It is not uncommon for patients to see their doctor and demand antibiotics, which may not always be needed in the case of a viral infection. On top of the over-prescribed, patients often misuse them by not taking the full dosage after seeing symptoms diminish. 

In microbiology, we learned that the efficacy of hand sanitizers is marginal as compared to traditional hand-washing (with soap); do you think that this may have an effect on resistant Influenza viruses?

No, in the case of Influenza, neither hand sanitizers nor hand-washing produce any type of resistance. 

Over the MANY misconceptions that exist about Influenza, what ones do you think are the most important to disprove and why?

So much of the general public believes that the flu is also the stomach flu (which is generally caused by the Norwalk Virus). A very large misconception. Another issue that is seen very frequently is people believing that the flu vaccine will give you the flu. This is ludicrous. People always say "As soon as I got the flu shot, I got sick with the flu." This could be the case, but the general public does not realize that there are only three strains of Influenza contained in the flu vaccine, which means that they could be infected with one of the other 100+ strains of Influenza that is out at any given point in time. This misconception is very hard to eliminate in the public because of their lack of knowledge about the flu itself.  

How successfully can Influenza exist outside the body (specifically on surfaces/inanimate objects)?

It varies from surface to surface but the CDC states that it is about 2-8 hours before Influenza succumbs to environmental stresses. The best way to disinfect is using alcohol, iodophors, or some other type of disinfectant. 

Finally, why is it important for students studying in Biology to learn about Influenza?

Most of the time you will become some type of health professionals so it will be important to know it then. Also, it is very important for students to learn about Influenza in order to spread the knowledge and educate the general public about Influenza. The vaccine is not able to prevent catching the flu 100% so it is important for students to be educated and help others to understand this. Influenza will be with us forever, it is the model for change, so the best way to prevent it is through education about it. 

                                                                                                           

So that's it, our interview about the flu. Did anything surprise you or catch your eye? I found it very interesting how evolution, even in something as simple as the flu, can play such a large role in developing new vaccines and treatments in modern medicine. I was also shocked how long the virus remains active on surfaces! It will make me think twice before touching the door handle into Massman after I've seen someone sneeze in their hand. Dr. Cooper was a wonderful person to interview and find out more on the flu without actually catching the flu! Reflecting on the interview, I am glad that we chose to do our grid computing project on Influenza. It's something that everyone has to deal with but a very few amount of people know a lot about. So hopefully this post educates you about Influenza, helping you know a little bit more than you did  yesterday. I'm going to end this post with this question: did you get your flu shot this year?

Introduction to the project

The Influenza Grid-Computing Project

In an evolution class at Rockhurst University we are required to do a learning service project.  This project had to involve contributing to a current grid-computing project. We chose to contribute to the Influenza Antiviral Drug Search. This grid-computing project is searching for new antiviral drugs for influenza that will stop the spread of new strains as well as strains that are currently showing drug resistance to antiviral drugs. 

In order to participate in this grid computing project please go to the following link: 

http://www.volunteerathome.com/active-projects/16-world-community-grid.html

What is influenza and why would new antiviral drugs be beneficial? 

Influenza is a single stranded RNA virus and is often referred to as the flu.  There are three major types of influenza which are type a,b, and c. Type a and b infects humans and animals.  Type c infects only animals. Each type contain many different strains that tend to change from year to year.  Influenza can be transmitted by direct contact with infected individuals, contact with contaminated objects and inhalation of respiratory droplets.  A few symptoms that typically occur once infected with influenza are fever, headache, shaking chills,cough, and shore throat. There are currently antiviral drugs that may reduce influenza symptoms that include Relenza, Tamiflu, and Amantadine Hydrochloride.  However, as was already stated some strains of influenza have become resistant to these antiviral drugs. This is one way in which new antiviral drugs would be beneficial in treating influenza. Another way that new antiviral drugs would be beneficial is by stopping the spread of new strains of influenza. 

To learn more about influenza and antiviral drugs please visit the following links provided:

http://www.cdc.gov/flu/antivirals/whatyoushould.htm

http://www.vdh.virginia.gov/Epidemiology/factsheets/Influenza.htm

http://www.webmd.com/cold-and-flu/tc/influenza-topic-overview

What is grid-computing? 

Grid computing is a form of networking and involves resources from many computers in a network being used at the same time to address a single problem or task.  In grid computing unused processing cycles of all computers in a network are used to solve problems too intense for any single computer.  The problems that are examined are usually of a scientific or technical nature.  Also the problems examined require a great number of computer processing cycles or access to large amounts of data. Several thousand computers can be involved in a grid computing project.  The computers involved in a grid computing project create what can be thought of as a virtual supercomputer. Different grid computing techniques can be used to create different types of grids. For example an equipment grid will use a grid to control a piece of equipment while a data grid will manage large amounts of information that many users share accesses to. 

To learn more about grid-computing please visit the following links provided: 
http://computer.howstuffworks.com/grid-computing.htm
http://www.webopedia.com/TERM/G/grid_computing.html
http://www.wisegeek.com/what-is-grid-computing.htm
http://searchdatacenter.techtarget.com/definition/grid-computing

TEM of negatively stained influenza virions.  Pictured obtained from: http://en.wikipedia.org/wiki/File:EM_of_influenza_virus.jpg

Structure of the influenza virus.  Picture obtained from: http://micro.magnet.fsu.edu/cells/viruses/images/influenzafigure1.jpg