Thesis

When I started working in Professor Tom Maniatis‘s lab, I was (foolishly) unaware of Maniatis’s role in writing (and doing the original methodology work for) the famous cloning manual Molecular Cloning: A Laboratory Manual, nor was I aware of his groundbreaking work on understanding the regulatory mechanisms of Lambda phage, nor was I even that interested in innate immunity (I had been under the impression adaptive immunity was where all the interesting research was), the topic he asked me to help two of his postdoctoral fellows research. Somehow, after three years of working in the lab (including one summer and many late nights), I not only conjured up enough data to put to paper, but picked up enough about the systems which regulate Interferon Beta to trick the thesis readers into giving me an A! Much of that has to do with the guidance and support from Ben tenOever, the postdoctoral fellow I worked with who is now doing very well as a professor at Mount Sinai, who tirelessly supported me through months of (failed) experiments and (probably stupid) questions.

Transcriptional Regulation of Members of the Tripartite Motif Family in Response to Viral

Abstract:

TRIM30 and TRIM34 are two proteins of the Tripartite Motif family which have recently been shown to be dependent on IKKe, a kinase implicated in the regulation of a subset of genes critical for innate immunity, for their proper transcriptional regulation. This study performs a functional analysis of the genes and finds evidence that the two genes help mediate a host cell’s antiviral state. This study also characterizes the transcriptional regulation of these genes finding that they are dependent on the cytokine Interferon Beta and on the Interferon Beta activated kinase IKKe for proper upregulation. The nature of this transcriptional regulation is tracked to a specific Interferon Stimulated Response Element in their promoter, and this evidence is used to conjecture based on network motif analysis the role of this and other genes involved in the host cell response to viral infection.

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