A Computational Model of Progressive Multifocal Leukoencephalopathy (Summary)

Over these past seven weeks of research, I’ve made so much progress on my models. More importantly,  I’ve learned a lot. I was able to study the JC virus infection cycle, how a variety of transcription factors affect viral replication and transcription, the body’s immune response, and potential PML treatments.

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A Computational Model of Progressive Multifocal Leukoencephalopathy (Update 3)

These past two weeks of research have been interesting, because rather than focusing on larger subtopics as in previous weeks, I was able to look at a greater number of smaller topics. I studied a wide range of transcription factors, including C/EBPB, Sp1, AP-1, YP1, Egr-1, SRSF-1, and NF-1. As Progressive Multifocal Leukoencephalopathy (PML) and the JC virus are still a relatively new discovery, some of these factors have limited research on them. Another problem I ran into was that some of these factors have been linked to the JC virus in literature, though the exact cellular mechanisms and interactions are unknown. Computational modeling directly relies on this knowledge, making my models for these factors less thorough than past transcription factors, like NFkB.

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A Computational Model of Progressive Multifocal Leukoencephalopathy (Update 2)

As my fourth week of summer research draws to a close, I wanted to provide another update on my progress. I’ve been working on a computational model showing the cellular interactions that allow the reactivation and spread of the JC virus, which is the cause of the opportunistic infection Progressive Multifocal Leukoencephalopathy. For the past two weeks, my primary focus has been on transcription factors and the role they play in viral infection. Specifically, I looked at transforming growth factor beta 1 (TGF-B1), tumor necrosis factor alpha (TNFa), and nuclear factor kappa beta (NFkB). All three of these factors promote viral transcription, furthering the spread of the JC virus throughout the body, and most devastatingly, the brain.

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A Computational Model of Progressive Multifocal Leukoencephalopathy (Update 1)

Today marks the start of my third week of on-campus research, so I wanted to provide an update about what I have accomplished so far. I have been working in Professor Coleman’s computational modeling lab, using the computer program Cell Designer to model the chemical reactions and pathways of neurodegenerative diseases. My focus is on Progressive Multifocal Leukoencephalopathy (PML), a relatively rare yet fatal opportunistic disease that can affect HIV/AIDS patients as well as immunosuppressed Multiple Sclerosis and Crohn’s Disease patients who are on certain medications.

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A Computational Model of Progressive Multifocal Leukoencephalopathy (Abstract)

Human Immunodeficiency Virus (HIV) and some treatments for autoimmune diseases such as Multiple Sclerosis (MS) and Crohn’s disease can result in a suppressed immune system. This opens up the possibility for further viral complications, including Progressive Multifocal Leukoencephalopathy (PML). Leukoencephalopathy quite literally means degeneration of the white matter of the brain, which is exactly what this disease entails. When the JC virus, which is dormant in at least half of the population, becomes active, it causes demyelination. This process involves damage to the myelin sheath, a fatty layer on nerve cells, therefore creating lesions that interfere with communication between neurons. Symptomatic expression of PML can vary, but most often presents as progressively worsening visual, cognitive, and motor deficits. Though this disease is relatively rare, affecting five in one hundred AIDS patients and four in one thousand MS patients who are on the medication natalizumab, its prevalence continues to increase with the use of drugs that modify immune response (Ferenczy et al., 2012). Furthermore, the lack of current treatment for PML has resulted in a mortality rate upwards of thirty percent, and it leaves survivors with lifelong impairment. Research on PML is imperative, which is why I hope to contribute to this effort by creating a computational model of PML and its cause, the JC virus.

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