Our work with The Lattice Project has definitely been fulfilling, and I plan to keep the program running on my computer to continue helping in whatever was we can.
Over the course of this project, we had 891 credits. Unfortunately, the Lattice Project did not give any more in depth information about the number of hours of work we had done, but we feel that we have done what we could for our part in helping our particular Grid Computing project.
Wednesday, May 2, 2012
Thursday, April 26, 2012
Question Responses
1. Why, from an evolutionary standpoint, might it be informative for scientists or doctors to study conditions in mice when investigating human diseases like Parkinson’s?
It is important for conditions such as Parkinson's to be studied in mice because it allows us to study the mechanism of the disease and test possible treatments in a timely manner without risking human life. In the scientific world, mice are considered model organisms because they are more prolific than humans and it is easier to follow inheritance through generations in mice than it is in humans because mice have a shorter generation time than humans. Mice also have a comparable genome to humans, so they are exemplary in many cases to see how gene manipulation in mice will affect humans. Also, when using mice in a lab, it is much easier and more ethical at this time to extract genes and manipulate the genomes of the mice.
2. Name five non-human taxa that are included in the results of the BLAST. What does this tell you about the Parkin gene?
Although there were many non-human taxa that were included in the results, five specifically mentioned were: Pongo abelii, or the Sumatran orangutan; Macaca fascicularis, the crab-eating macaque; Sus scrofa, the wild boar; Equus caballus, the wild horse; and Mus musculus, the common mouse. Clearly, this tells us that many non-human taxa contain the Parkin gene or a Parkin-gene analog. Because of this, we believe that the mitochondrial health of these organisms depends on the Parkin gene, like we have seen in humans. As is seen in the paper that we reviewed, the Parkin gene works with the PINK1 gene to maintain mitochondrial health and destroy unhealthy mitochondria to prevent a build up of free radicals that signals for neuronal cell apoptosis. In the case of humans, this neuronal apoptosis causes an onset of familial Parkinson’s disease. Because so many taxa have the Parkin gene, it can be helpful for laboratory testing and genetic research to see the effect of gene manipulation and mutation, and how these mutations may have an effect on Parkinson’s disease itself.
3. Is Parkinson’s subject to natural selection? Why or why not?
It is important for conditions such as Parkinson's to be studied in mice because it allows us to study the mechanism of the disease and test possible treatments in a timely manner without risking human life. In the scientific world, mice are considered model organisms because they are more prolific than humans and it is easier to follow inheritance through generations in mice than it is in humans because mice have a shorter generation time than humans. Mice also have a comparable genome to humans, so they are exemplary in many cases to see how gene manipulation in mice will affect humans. Also, when using mice in a lab, it is much easier and more ethical at this time to extract genes and manipulate the genomes of the mice.
2. Name five non-human taxa that are included in the results of the BLAST. What does this tell you about the Parkin gene?
Although there were many non-human taxa that were included in the results, five specifically mentioned were: Pongo abelii, or the Sumatran orangutan; Macaca fascicularis, the crab-eating macaque; Sus scrofa, the wild boar; Equus caballus, the wild horse; and Mus musculus, the common mouse. Clearly, this tells us that many non-human taxa contain the Parkin gene or a Parkin-gene analog. Because of this, we believe that the mitochondrial health of these organisms depends on the Parkin gene, like we have seen in humans. As is seen in the paper that we reviewed, the Parkin gene works with the PINK1 gene to maintain mitochondrial health and destroy unhealthy mitochondria to prevent a build up of free radicals that signals for neuronal cell apoptosis. In the case of humans, this neuronal apoptosis causes an onset of familial Parkinson’s disease. Because so many taxa have the Parkin gene, it can be helpful for laboratory testing and genetic research to see the effect of gene manipulation and mutation, and how these mutations may have an effect on Parkinson’s disease itself.
In most cases, in non-familial Parkinson’s disease,
it is not subject to natural selection because it does not affect a patient’s
fitness. In the majority of cases, Parkinson’s develops after the
child-bearing years of the patient. In the case of familial Parkinson’s
(discussed in our paper), we believe that this form of Parkinson’s disease can
be subject to natural selection. In the familial form of the disease, it
is possible for patients to develop the disease at a much younger age and pass
the defective Parkin gene to their children. This early-onset Parkinson’s
can indeed have an effect on the fitness of the patient. If the effect on
fitness is extremely detrimental, then natural selection will act on the
disease, and the Parkin gene will be selected against.
4. Refer to the last paragraph of the Results and Discussion (pages 5&6). Discuss selection for and against the defective mitochondria associated with PINK1 mutant cells.
Bonus: What types of mutations are described in the second column of Table 1 (SNPs, substitutions, indels, missense, nonsense, transitions, transversions, etc.)?
Defective mitochondria can be positively selected for in certain
circumstances, which are associated with anaerobic metabolism.
1. If
muscle tissue does not receive enough blood supply to prevent anaerobic
metabolism, it is subject to more stress than in normal circumstances. This
type of environment is more prone to mitochondrial disease, so defective mitochondria
are therefore positively selected for.
2. In
the central nervous system, normal mitochondria are required in order to
convert non-glucose fuel such ketone bodies. This is especially important in
infancy, when the CNS requires more fuel to facilitate growth, or during
periods of fasting, when glucose is not readily available. While normal
mitochondria are converting, defective mitochondria have a replicative
advantage during these times.
3. During
fetal life, anaerobic metabolism maintains relatively low levels of pH and Po2,
which gives defective mitochondria a selective advantage over normal
mitochondria (Clarke, 1990).
Defective mitochondria are
selected for in familial Parkinson’s disease, which we have seen in this paper.
The mutated PINK1 gene impairs normal mitophagy, which gives mutated
mitochondria an advantage, due to a decrease in the removal of defective
mitochondria.
Defective mitochondria can also
be selected against, which has been observed in normal physiology. Normally,
defective mitochondria are selected against during the process in which PINK1
and parkin remove defective mitochondria by mitophagy.
The mutations described in the second column of Table 1 are substitutions. The shorthand on the table is denoting the chromosomal location and then the substitution caused the mutation (ex: C > G, which would denote cytosine to guanine).
Monday, April 16, 2012
Wednesday, March 21, 2012
Emily Mitchell - Interview Reflection 3/21/2012
1. Describe your feelings about or response to the interview.
I really enjoyed talking to Dr. Weinstein, and I thought the interview went very well. He was very helpful and although he had never heard of grid computing, he was enthusiastic to learn about it and contribute. As a neurologist, I knew he would have a background in diseases like Parkinson's, but I found that he had such a large amount of knowledge about Parkinson's and really enjoyed learning new things about the disease.
2. What changes occurred for you as a result of your interview?
Dr. Weinstein talked a lot about how much the increase in the average lifespan has an effect on neurological diseases like Parkinson's disease. He explained to us that as we age, the frequency of disease due to protein misfolding increases, and so there is a higher prevalence of people with diseases like Parkinson's. I had never considered this, but it made me realize just how much each generation changes major health concerns. This also made me think about how medicine has to change with each generation depending on other factors such as lifestyle, lifespan, etc.
3. Did anything about the interview disturb you?
The thing that disturbed me during the interview was how misinformed the public is about diseases. Dr. Weinstein said that a lot of people he has come into contact with have a misconstrued idea about the cause of neurological diseases, which prevents them from being able to take preventive measures. I think this is a major concern, especially because there is probably a higher percentage of people with neurological diseases such as type II diabetes, and there are ways to help prevent them if the public is well-informed.
4. Describe the connections you found between the interview and your research & classwork.
There were a lot of connections between the interview and our classwork, both on a molecular and population level. The mutations and protein misfoldings that lead to neurological disease had a lot to do with what we had studied in class about mutations and their effect on a population. It also made me consider how although protein misfoldings linked with Parkinson's and some other neurological diseases occur after reproductive age, there are probably some diseases, perhaps type II diabetes, in which mutations and protein misfoldings occur during reproductive age. If this is the case, this could have a huge effect on the population. This relates to our discussions in class about population genetics and the effects of microevolution on a population.
1. Describe your feelings about or response to the interview.
I really enjoyed talking to Dr. Weinstein, and I thought the interview went very well. He was very helpful and although he had never heard of grid computing, he was enthusiastic to learn about it and contribute. As a neurologist, I knew he would have a background in diseases like Parkinson's, but I found that he had such a large amount of knowledge about Parkinson's and really enjoyed learning new things about the disease.
2. What changes occurred for you as a result of your interview?
Dr. Weinstein talked a lot about how much the increase in the average lifespan has an effect on neurological diseases like Parkinson's disease. He explained to us that as we age, the frequency of disease due to protein misfolding increases, and so there is a higher prevalence of people with diseases like Parkinson's. I had never considered this, but it made me realize just how much each generation changes major health concerns. This also made me think about how medicine has to change with each generation depending on other factors such as lifestyle, lifespan, etc.
3. Did anything about the interview disturb you?
The thing that disturbed me during the interview was how misinformed the public is about diseases. Dr. Weinstein said that a lot of people he has come into contact with have a misconstrued idea about the cause of neurological diseases, which prevents them from being able to take preventive measures. I think this is a major concern, especially because there is probably a higher percentage of people with neurological diseases such as type II diabetes, and there are ways to help prevent them if the public is well-informed.
4. Describe the connections you found between the interview and your research & classwork.
There were a lot of connections between the interview and our classwork, both on a molecular and population level. The mutations and protein misfoldings that lead to neurological disease had a lot to do with what we had studied in class about mutations and their effect on a population. It also made me consider how although protein misfoldings linked with Parkinson's and some other neurological diseases occur after reproductive age, there are probably some diseases, perhaps type II diabetes, in which mutations and protein misfoldings occur during reproductive age. If this is the case, this could have a huge effect on the population. This relates to our discussions in class about population genetics and the effects of microevolution on a population.
Jessica Lloyd's Response to the Interview
1. Describe your feelings about or response to the
interview.
I felt that the interview was very
informative. I have two family members
that have Parkinson’s disease, so it was nice to learn about the doctor’s
perspective on the disease. I liked that
Dr. Weinstein was so willing to talk to us; he seemed genuinely passionate
about his work and about educating the public about the facts about Parkinson’s.
2. What changes occurred for you as a result of
your interview?
The
interview helped me to realize how important a role protein misfolding plays in
the development of Parkinson’s. Like
most of the general public, I assumed that genetics played a distinct (albeit
unknown) role in the development of Parkinson’s. Hearing Dr. Weinstein explain how the drugs
used to treat Parkinson’s counteract the symptoms resulting from protein
misfolding really opened my eyes about the potential causes of this
debilitating disease.
3. Did anything about the interview disturb you?
What disturbed me about the interview, is when
Dr. Weinstein was asked about whether evolution was important in his field, he
promptly answered no. This surprised me
because in class we have talked about how important understanding evolution is
to medicine. This was especially disturbing
to hear, because since Parkinson’s disease results from protein misfolding, it
would logically follow that evolution would play a part in the mutations
leading to protein misfolding.
4. Describe the connections you found between the
interview and your
research & classwork.
What I learned about protein misfolding from the
interview was very similar to what I learned about in my Genetics, Cell
Biology, and Molecular Biology classes.
The difference is that I had not applied this line of thinking specifically
to Parkinson’s before the interview. I
also thought it was great how large an impact grid computing can play in
researching how proteins are folded.
From my classes, I have learned how important proteins are to the life
and development of our bodies, so it is great to learn that something so simple
as running a program on your computer can increase our understanding of protein
structure and function.
Monday, March 19, 2012
Abby Thuet's response to interview:
1. Describe your feelings about or response to the interview.
I had never met a neurologist before, so before having this interview, I did not know what to expect. Dr. Weinstein was just one doctor in a practice containing multiple neurologists, and he was incredibly nice from the moment we arrived for the interview. Something that I definitely noticed was that he was incredibly professional and business-like, which made the interview go very smoothly.
Something very positive about the experience was that he was very willing to answer any questions that we had. Whenever I apologized about our inconvenience or thanked him for everything he was doing for us, he kept repeating over and over again that he was more than happy to be doing it, and he expressed that we could call him if we thought of anything else, or if later in the semester any other questions came to us. It was refreshing because he had such a professional attitude, but was still very good at making sure that we were comfortable with the interview.
2. What changes occurred for you as a result of your interview?
I really enjoyed talking to Dr. Weinstein because he made me realize that a lot of the reasons that he wanted to be a doctor are reasons that have also led me to my choice to attend medical school after Rockhurst. Between the desire for the intellectual aspect of science and medicine, the desire to help others, and the enjoyment that comes from using deductive reasoning to solve problems that may seem unsolvable, it reaffirmed that I have made the decision about my future for all of the right reasons.
This interview made me realize even more how important the mechanisms our body uses to fold proteins correctly are. It baffles me that our bodies are able to do all of these amazing things and send these signals and make these proteins without any conscious effort from us. Also, it is unbelievable that just a small problem, or even a single change in an amino acid can cause for a disease or debilitating problem.
Something that also interested me that I realized after this interview is that many more people than I realized know about and support grid computing. Since I had never heard of it before, I guess I had naively thought that if I didn't know about it, many people did not. But in talking to Dr. Weinstein, I realized that grid computing is something that most doctors and researchers completely support and hope to further this research in whatever ways they can.
3. Did anything about the interview disturb you?
Something that Dr. Weinstein said in the interview was incredibly interesting to me. When I asked him if he thought that evolution was important in his field, he answered with a quick no. He didn't offer any more of an explanation, and after that, he asked what the next question was. It just surprised me because I know that from what I have learned in this class, there are definite applications for neurology and Parkinson's disease. This is especially true because Parkinson's disease includes protein misfolding, and we have spent so long in class talking about mutations, which can cause this misfolding. After the interview I had to think about this answer for awhile, and I came to the conclusion that it is possible that he had never or not recently taken any classes on or read any papers on the importance of evolution, and its applications in science and medicine. I believe that if he did, his answer would have changed to a resounding yes.
4. Describe the connections you found between the interview and your research & classwork.
Something that we have talked about extensively in Evolution is mutation. We have learned of the many different types of mutations as well as how seemingly simple mutations that cause things like frameshift mutations can cause debilitating diseases. Parkinson's disease is caused by mutations in specific genes, and those mutations cause the protein misfolding that is characteristic of Parkinson's disease. This interview truly caused me to realize how intricately our proteins our made, and how important it is that they are made correctly. I believe that this interview was incredibly informative, and beyond understanding Parkinson's a bit more, it also reinforced my belief in my future as a physician, for which I am incredibly grateful.
I also realized because of this interview how important grid computing is. It is such a simple thing to let these programs run in the background of your computer, and it can be so helpful to the world of research. Because of this interview and what we have talked about in class, I realize that I have no problem with letting this program run indefinitely on my computer, as long as it is still helping the cause. Dr. Weinstein really helped me to come to this conclusion because he was just reinforcing how helpful these programs can be, and how easy it is for anyone to do.
Friday, February 17, 2012
Interview Write-Up
On February 14th, 2012, the three of us interviewed Dr. Weinstein, a
neurologist at Neurological Consultants of Kansas City in Overland Park
After explaining our grid computing project to Dr. Weinstein, he said that he had never heard of grid computing, but that he thought it sounded like a great way to advance protein misfolding research. It is important that people know about protein misfolding, he said, because our lifespan is older than it used to be, which has led to an increase in mutations and protein misfoldings. There is a higher frequency of disease due to protein misfolding in older individuals, and the general public should be aware of this. Diseases caused by protein misfoldings are not limited to neurodegenerative diseases, like Parkinson’s and Alzheimer’s; protein misfoldings can also cause nonneurological diseases such as type 2 diabetes. Dr. Weinstein said that health education is important so that the public is not misinformed about the causes of diseases and can start taking preventive steps.
This led us to ask about common misconceptions that the public might have about Parkinson’s. Dr. Weinstein said that many people think that Parkinson’s disease is mostly hereditary and that it is affected by lifestyle. Only a small percentage of people with Parkinson’s develop the disease due to genetics, and usually it is early onset Parkinson’s. Lifestyle might play a role in causing the disease, he said, but the main culprit is protein mutation and misfolding.
Dr. Weinstein decided on his career in medicine because he enjoyed not only the academic aspect of science, such as the intellectual challenge and taking exams, but also because he was fascinated by the way medicine uses deductive reasoning to solve problems and help people. He was particularly interested in neurology because it requires a great deal of reasoning and innovation, and the field is rapidly developing new technologies for the treatment of neurological disorders.
This led us to inquire about specific treatments that are commonly used to treat Parkinson’s. Dr. Weinstein said that the most common treatment is a combination of the drugs Levadopa and Carbidopa. Levadopa is in a class of drugs called central nervous system agents, and works by converting to dopamine when metabolized by the body. Carbidopa is in a class called decarboxylase inhibitors, and works to lessen the side effects caused by Levadopa and to ensure Levadopa does not break down before reaching the brain. Another common treatment that Dr. Weinstein mentioned was dopamine agonists, which act as false transmitters and are similar to Levadopa, but are less potent.
Dr. Weinstein discussed current research and new treatments for Parkinson’s, namely surgical treatments for dyskinesia, a movement disorder that consists of involuntary movements or diminished voluntary movements associated with Parkinson’s disease. The surgery basically involves deep brain stimulation in the thalamus to reduce dyskinesia and greatly improves a patient’s quality of life.
The interview with Dr. Weinstein increased our knowledge about Parkinson’s disease and the treatments that are currently being used, as well as new treatments that are being developed. We also learned that our grid computing project goes beyond the scope of Parkinson’s disease because of the numerous diseases caused by protein misfolding. Dr. Weinstein gave us some new insights about how medicine is changing as our population ages, and the many ways protein misfolding research can benefit people.
A special thanks to Dr. Weinstein for agreeing to be interviewed for this project, and to better our understanding of Parkinson’s disease and protein misfolding.
After explaining our grid computing project to Dr. Weinstein, he said that he had never heard of grid computing, but that he thought it sounded like a great way to advance protein misfolding research. It is important that people know about protein misfolding, he said, because our lifespan is older than it used to be, which has led to an increase in mutations and protein misfoldings. There is a higher frequency of disease due to protein misfolding in older individuals, and the general public should be aware of this. Diseases caused by protein misfoldings are not limited to neurodegenerative diseases, like Parkinson’s and Alzheimer’s; protein misfoldings can also cause nonneurological diseases such as type 2 diabetes. Dr. Weinstein said that health education is important so that the public is not misinformed about the causes of diseases and can start taking preventive steps.
This led us to ask about common misconceptions that the public might have about Parkinson’s. Dr. Weinstein said that many people think that Parkinson’s disease is mostly hereditary and that it is affected by lifestyle. Only a small percentage of people with Parkinson’s develop the disease due to genetics, and usually it is early onset Parkinson’s. Lifestyle might play a role in causing the disease, he said, but the main culprit is protein mutation and misfolding.
Dr. Weinstein decided on his career in medicine because he enjoyed not only the academic aspect of science, such as the intellectual challenge and taking exams, but also because he was fascinated by the way medicine uses deductive reasoning to solve problems and help people. He was particularly interested in neurology because it requires a great deal of reasoning and innovation, and the field is rapidly developing new technologies for the treatment of neurological disorders.
This led us to inquire about specific treatments that are commonly used to treat Parkinson’s. Dr. Weinstein said that the most common treatment is a combination of the drugs Levadopa and Carbidopa. Levadopa is in a class of drugs called central nervous system agents, and works by converting to dopamine when metabolized by the body. Carbidopa is in a class called decarboxylase inhibitors, and works to lessen the side effects caused by Levadopa and to ensure Levadopa does not break down before reaching the brain. Another common treatment that Dr. Weinstein mentioned was dopamine agonists, which act as false transmitters and are similar to Levadopa, but are less potent.
Dr. Weinstein discussed current research and new treatments for Parkinson’s, namely surgical treatments for dyskinesia, a movement disorder that consists of involuntary movements or diminished voluntary movements associated with Parkinson’s disease. The surgery basically involves deep brain stimulation in the thalamus to reduce dyskinesia and greatly improves a patient’s quality of life.
The interview with Dr. Weinstein increased our knowledge about Parkinson’s disease and the treatments that are currently being used, as well as new treatments that are being developed. We also learned that our grid computing project goes beyond the scope of Parkinson’s disease because of the numerous diseases caused by protein misfolding. Dr. Weinstein gave us some new insights about how medicine is changing as our population ages, and the many ways protein misfolding research can benefit people.
A special thanks to Dr. Weinstein for agreeing to be interviewed for this project, and to better our understanding of Parkinson’s disease and protein misfolding.
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