Link to statistics

https://secure.worldcommunitygrid.org/ms/viewMyMemberPage.do

Samantha Keeling,

            Boxing cans, serving up soup, or helping out in a daycare are typical images one conjures up when thinking about service projects. This semester in evolution class, we had a chance to do a whole new style of service. We contributed to research through grid computing. We downloaded some software and throughout the semester we have been contributing to the World Grid. It is kind of mind boggling to think that we are helping researchers learn more about diseases just by letting some software run on your computer.

            Our group chose to learn more about Parkinson’s disease. From learning exactly what a grid is, to reading a research article on Parkinson’s I have learned a lot about the disorder. Overall the entire experience has been very enlightening

Marium Choudhry

            This class has given me the opportunity to provide to our community whilst learning about a new disease as well. In evolution our group was introduced to the concept of grid computing. Through this software we contributed to the energy that researchers need to conduct their studies. We were also able to learn more about Parkinson’s disease by posting on the blog every few weeks about new findings or interviews that we had done. I find it important to be aware of such diseases since it has become a growing issue. While the first part of the semester consisted of us gathering info and learning more about the disease, we were able to analyze research that had been done about the disease and then also were able to use the information to relate to evolution.

Zach Kramer,

During this semester in our evolution class, we have been able to assist in research for Parkinson’s disease during a service learning project. This semester of work has been very systematic and eye opening. We started the semester by just getting the basic information of Parkinson’s disease and grid computing, to receiving more precise information from an expert in the field. And to cap off the semester, we finished by relating the information we had learned during the project to the information we had learned in the class.

And all that had to be done to help research in the field of Parkinson’s was to have a program run in the background. Advances in technology like this can further research in many fields of medicine and science as a whole. By the combined power of a program running on many computers, the ability is more powerful than a supercomputer. This illustrates how we as a society can and should come together because together we are stronger/smarter than when we are separate. Through continued projects such as this one, diseases which have plagued mankind for too long will soon meet their end. 

Andrew Martin

I was glad that our group chose Parkinson's disease because it is a disease that is greatly affecting the elderly population in America. It is a disease that we have not found a definitive cause, nor cure for so joining in on the grid computing network we hoped to find one of these factors. I had a grandparent that suffered from Parkinson's and I'm sure there are several other people in the class that have known someone go through this disease. It is a very debilitating disease because they slowly lose the things that made them independent. Whether that may be being able to control their walking and grabbing motions, to even being able to form words. Parkinson's slowly degenerates their brain until they are essentially locked into their body. Because it is more likely to happen to the older generation (the numerous number of "baby boomers") this is a disease that I will most certainly come in contact in my medical career. Maybe through grid-computing it will not be such a mystery by the time I'm treating patients.

Sean Steinmetz        

 In this semester’s evolution course, my group and I are participated in our first ever grid computing project with Parkinson’s research as our subject of choice.  Grid computing, a constantly running algorithm that uses the CPU and data of one’s laptop combined with many others to run mathematical experiments, was a great way to first learn about what Parkinson’s was and to then help in researching a cause, and hopefully a cure.

               As the semester went on, we learned more and more about the complexities of the Parkinson’s disease, and we even got to interview an expert in the field of neuroscience, Rockhurst’s very own professor Sturgill.  With all the information amassed and the concepts that we have learned in class, our group began to understand the evolutionary background of the development of diseases, specifically Parkinson’s.  Using the grid computing software and doing a bit of our own research, we gained insights into how scientists are currently working to fight burdensome and life-threatening disease and illness, and most of it rests on the shoulders of ordinary people simply participating in these many grid computing projects.  Continued use of this technology will open the door to a massive amount of data that can be used to advance the fields of medicine and science as a whole, and will lead to a healthier, safer tomorrow.

The following questions give insightful information obtained from the article Ancient origin of the Parkinson disease gene LRRK2

1. Based on our discussion of paralogous genes in class, how do you think the Roco family of genes originated?  Do we see deep homology in this gene family?  How do you know?

Although the majority of organisms that have LRRK genes from the Roco family are vertebral deuterostomes, protostomes lacking vertebrae have also been shown to have genes that are paralogous to the ones in more complex deuterostomes, including humans.  The fact that these genes exist, but in simpler form, in organisms that came earlier in our evolutionary history shows a close linkage of this family of genes in a wide range of species.  One species in particular, the sea anemone Nematostella vecentis, a cnidarian organism, showed to have the most complex set of LRRK genes described in any animal, thus far.  This species is ancient and these genes must have developed long ago in its evolution.  Also, the LRRK2 gene of N. vecentis is an exact paralog to the human LRRK2 gene, showing direct evolutionary linkage between the two.  A very simple form of a Roco gene – containing a Roc, COR, and Kinase domains – must have first formed in protostomes closely related to N. vecentis and through the process of gene duplication errors during meiosis, must have created several forms of these types of genes, similar to the evolution of the hemoglobin paralogous gene family.

Because we see forms LRRK and other Roco family genes in all vertebrate deuterostomes, as well as some protostomes, such as insects, the origins of this gene family must extend far back in the evolutionary timeline.  The existence of this gene family in both highly organized, complex vertebrates, as well as simpler, less complex non-vertebrates shows both deep homology and an ancient origin of the gene family.

2. According to the author, are the LRRK2 genes in humans and sea anemones orthologous? In figures 3 & 4, are the LRRK2 genes from these two species in the same clade?

Species are orthologous when they are different but evolve from a common ancestral gene. When researching the genome of Cnidarians, the author saw the relationship between the human and sea anemone LRRK2 genes. Although the LRRK2 gene was at first thought to have arrived through duplication, it was later discovered that the LRRK2 gene was one of two duplications that occurred before the protostome-deuterostome split. Because of the two duplications, LRRK1, LRRK2, and LRRK3 genes were now produced. Vertebrates retained the LRRK1 and LRRK2 gene while protostomes only had the LRRK3 gene. All three genes were present in Cnidarians, sea anemones, starfish, and Echinoderms. In figure 3 and 4 it can be seen that the LRRK2 genes from both Homo sapiens and Nematostella Vectensis are found in the same clade. 

3. Both types of PD (familial and sporadic) involve the human LRRK2  gene. Differentiate between these two types and briefly discuss the role of LRRK2 in each.

Individuals with Familial Parkinson’s have a history of the disease in their family. On the other hand, Sporadic Parkinson’s disease occurs randomly and does not seem to run in families. Sporadic Parkinson’s disease is the more common form. Both types of Parkinson’s Disease involve the human LRRK2 gene. It was found that dominant mutation in LRRK2 may explain 13% of the familial PD cases and 5% of the sporadic PD cases. It has been found that LRRK2 orthologs have an Arm-like surface. Researchers have found that mutations in this surface have been involved in familial PD.  In both Sporadic and Familial Parkinson’s Involvement of LRRK2 gene is believed to play a role in dopaminergic cell death and the onset of the disease. In previous studies on non-human subjects the loss-of-function mutations in LRRK2 is what leads to dopaminergic cell death. It is unknown if this is the case for humans as well. This study suggests that increased/constitutive activity of the LRRK2 protein (probably through increased kinase function) is what leads to the loss of dopaminergic cells in patients with PD.  

4. Is it parsimonious for the author (page 10-11) to assume that LRRK3 was present in all eumetazoans and then lost in vertebrates?  What would be an alternative hypothesis?

Parsimony is the principle which tells us to choose the simplest scientific explanation that fits the evidence we have collected. And in the terms of looking at phylogenic tress, the best hypothesis is the one that requires the fewest evolutionary changes. When looking at Figures 3 and 4, we can address the question of which phylogenic treat is more parsimonious. In Figure 3, LRRK3 diverges earlier on from what would later end up being LRRK1 and LRRK2. This demonstrates the author’s belief that the LRRK3 gene was maintained in cnidarians, echinoderms, and protostomes, but it was lost in vertebrates. In Figure 4, however, LRRK2 diverges early to leave LRRK3 and LRRK1 to break away from each other at a later point. This shows another hypothesis which is that the LRRK3 gene is eventually lost in both the LRRK1 and LRRK2 genes. To determine which hypothesis was the better fit, we looked at the least complicated phylogenic tree with the fewest evolutionary changes. For Figure 3 and 4, although both possible, Figure 3 was the most parsimonious. But with the work of any phylogeny, more work could be performed to add more extension to the trees, creating a better, more parsimonious outcome about how these genes correspond with one another.

5. Why is it important to study protein folding/misfolding in Parkinsons, even though we know the genes that are responsible? 

            Studying the effects of protein folding are extremely important, even though we already know the cells that are affected by Parkinson’s Disease (LRRK1 & LRRK2). There is increasing evidence that states Parkinson’s, Alzheimer's , and even Huntington’s may all have a common root to the problem, protein folding. If the proteins do not fold into the correct shapes, they disrupt cellular function (whatever that may be) and cause clumps. In each disease they are called something different but for Parkinson’s Disease, they are called “Lewy bodies”. Studying the protein folding has many applications such as better explanations of how the disease starts, worsens, or spreads, as well as different treatment strategies based on the misfolded proteins.

         Looking at Mad Cow Disease, may better lead to our understanding of how these misfolded proteins can spread throughout the brain. For people with MCD, they have little bodies called prions which go around misfolding every protein that it comes in contact with. If Parkinson’s or Alzheimer’s has a similar mode of spreading to other cells, it would explain why these diseases are progressively degenerative in nature. Thinking about how the proteins fold can give us new methods of treatment, as well as an opportunity to continue uproot the cause of these neurodegenerative diseases.   

Interview with Dr. William Sturgill, Ph.D.

Professor of Psychology at Rockhurst University

We interviewed Dr. Sturgill, a professor of psychology at Rockhurst University to get his perspective of Parkinson's disease, and to shine some light on a still difficult disease. Here are both the questions we asked and his responses to the questions:

Why did you choose to go into the field of neuroscience?

I think the brain is the most fascinating object in the world to study, and yet, also the most difficult. It [the brain] is the most complicated organ ever produced. To put it in perspective, the cerebellum of the elephant is the best rival of the human brain. The elephant trunk alone has 50,000 muscles in it. So for the trunk to be able to do normal things, like eating and drinking, takes an amazing amount of fine muscular control given by the elephant's brain.

What experience have you had in dealing with patients with Parkinson's disease?

I don't have much experience dealing with Parkinson's in particular.

Are there any interesting stories that you have from your experience treating Parkinson's patients?

I performed studies involving humans and the inability that some have to detect a joke because of brain damage. Some of the patients may have had Parkinson's disease, while the vast majority had suffered from a stroke.
Besides the inability of detecting a joke, you can tell someone has Parkinson's from hypokinesis. Hypokinesis is the absence of voluntary movement which shows in the person's posture. They are frozen in place and can't seem to initiate movement. They have little tricks to "kick start" movement, however. Self-initiation is hard, but if a person is externally exposed to a target, they can initiate a "kick start". An example of this is when a person with Parkinson's walks with a can. They don't need the cane for pain relief; they need to be able to "kick start" movement. Also, persons with Parkinson's can be seen having tremors in their hands when they are at rest.

Why is it important for a doctor or researcher studying or treating Parkinson's disease to understand evolutionary development?

It's extraordinarily important when thinking about viruses or bacteria which evolve so quickly, but, in the case of Parkinson's, the systems that control movement have evolved over millions of years. And it's just as interesting to see how it work and what evolved. This whole "brain thing" is something that's evolved and has been doing so since even the lowest forms of life. These mechanisms have been evolving for millions of years. If you look at humans, you see this ability of an enormous complexity of movements. We need something to be able to perform one particular movement at a particular time over other options. This is done because of the complexity and ability involved in the brain.

What proteins/genes are involved in the development of Parkinson's disease?

I am not sure what genes are involved but the structures involved are the areas of the spinal chord, mid brain, and the brain stem. In the ventral mid brain, there is a dark substance called substantia nigra. This is where dopaminergic cells reside, generating dopamine which are connected to the basal ganglia. That's what sends messages to striatum and the excitatory messages which helps balance motor movements. Like any cells, as you age, those neurons in substantia nigra start to die off.  So when they start to die, Parkinson's disease is a result.

Have you heard of grid computing before? If so, how important is it in the research of Parkinson's and the development of a cure? 

I have not heard of grid computing before.

What are the current treatments for Parkinson's disease, and how do they work?

Some people's cellular atrophy happens faster than others. It may be because of a diet that is low in amino acids, including tyrosine. There are currently different options of treatment. One is to get L-Dopa, a precursor in the synthesis of dopamine. In processes in the body, the L-Dopa turns into dopamine. It calms people down but comes with consequences. Long term use cause harder jerks and hyper movement. In the last decade or so, people have been doing deep brain stimulation. They implant electrodes/stimulators which generate tiny bits of electricity on the striatum. Then the pulses are sent to the striatum, generating excitatory post synaptic potentials.

Around what age does the onset of Parkinson's disease begin?

Around the ages of 70 or 80, but there is the potential for it to happen earlier.

Reflections over the Interview

It was interesting to get more of a scientific view of Parkinson's disease, as a whole. From what causes it to the potential treatments, Parkinson's disease is an illness which pains many, many people. It was cool to hear about some of the research being done in trying to right the wrongs which Parkinson's disease creates. From the L-Dopa treatments to the deep brain stimulation, research is being done to trying and help alleviate the stress Parkinson's disease makes. It was disturbing to learn about how Parkinson's disease seems like an unavoidable outcome of age. Yes, there are ways that a person can get the disease when they are younger in life, but it seems that the older a person gets, the higher their chances of getting Parkinson's disease become. Being that we are part of an evolution class and the necessity to see how this connects with evolution, it was interesting to talk to Dr. Sturgill about the evolution of life and the evolution of the brain. Ever since the creation of the brain, there have always been problems with it too. It seems every time the brain evolves, from the lowest life forms to now, diseases, like Parkinson's disease evolve with it. But hopefully, through work in the grid computing system, we will be able to help in the research to stop the disease.

Grid Computing and Parkinson's Disease Introduction

Grid Computing is basically a network of regular computers, not in the same physical location, but connected still with the goal to solve some kind of "Great Problem". These problems are basically a set of fundamental problems with broad applications that can be solved with high-speed computing. A few of examples of these problems would be climate predictions, protein folding, or business algorithms. When someone uses the equipment the user is allowed to browse and check out their possible interest to help. Once the person has chosen their computer will be assigned some kind of task, like the rest of the computers in the same area. The computer will send data to some mass virtual file until the job is complete then the computer's program will stop running. Grid computing is supposed to be the next big technological break-through in varying parts of science, economics, and medicine.

We have chosen to do our group project over Parkinson's Disease. Parkinson's is a progressive disorder in the nervous system that affects movement. It's classic first identifier is a slight tremor in one's hand. As it progresses speech is often weakened or slurred and it will seriously limit a person's movement. Often times people lose automatic movements like smiling or swinging their arms when they walk. Unfortunately, there are eventual problems with thinking, swallowing and even sleeping. There is currently not a cure for Parkinson's but with proper diagnosis symptoms can be noticeably reduced. Someone is vulnerable to developing Parkinson's is when their dopamine levels become too low and abnormal brain activity begins. The exact cause is hard to say, it may be an environmental factor, a genetic mutation, or the presence of lewy bodies. In general, men, especially ones on the more elderly side, are the most prone to Parkinson's Disease. The Parkinson's Disease Foundation estimates there are probably 7-10 million people living with Parkinson's right now. In America, about 60,000 new people are diagnosed with Parkinson's, keep in mind, many go unreported. We are hoping our grid-computing project will help identify a causative agent for Parkinson's so that further advancements in treatment will we possible.