Jeremy Bird

Biological Sciences

Jeremy Bird

Assistant Professor

jgbird@udel.edu

302-831-1332

Office: 324 Wolf Hall

Resources and Links

Jeremy Bird's Google Scholar Publications

Education

BS - Loyola University in Maryland
PhD - Cornell University
Post-doctoral - The Waksman Institute of Microbiology, Rutgers University

Research Interests

Regulation of gene expression is essential for development, response to environmental signals, and prevention of disease states. Transcription is the first, and most highly regulated step in gene expression. Transcription consists of three distinct phases: initiation, elongation, and termination. The first phase, initiation is the most highly regulated as many factors including DNA structure, binding of transcription factors and availability of substrate all contribute to the decision to begin transcribing RNA. Most cellular transcription is performed by multisubunit RNA polymerases (RNAPs), which are conserved in sequence, structure, and function from bacteria to humans. In addition, organelles such as the mitochondria rely on single subunit RNAPs that are also highly conserved across eukaryotic organisms. Biological functions of the cell such as metabolism and gene expression are inextricably linked. My lab uses both traditional genetic and biochemical analysis as well as novel next generation sequencing methods to address fundamental questions about the interplay of metabolic state of the cell and transcription as the first step in gene expression.

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Recently, my work has focused on the discovery that many RNAs contain 5ʹ-caps comprised of cellular metabolites such as NAD(H) and dpCoA. I have established that RNAP utilizes these metabolites as non-canonical initiating nucleotides (NCINs) for transcription initiation in a promoter sequence-dependent manner. I also demonstrated that these caps have functional consequences, including increasing RNA stability. Building on my work establishing NCIN-mediated initiation in bacteria, I have also determined that mitochondrial RNAPs can utilize NCINs much more readily than multisubunit RNAPs and mitochondrial RNA products detected in vivo show much higher levels of capping than previously seen in bacteria. Additionally, I demonstrated that the redox state of the NAD(H) cap is dependent on cellular metabolic conditions, indicating that NAD-capping may provide a layer of epitranscriptomic regulation of gene expression by serving as a redox state sensitive switch. This novel mode of ab initio RNA-capping has broad implications for our understanding of how cells regulate gene expression and the level of transcription. The most tantalizing prospect is that this is a potential mechanism for regulatory crosstalk between metabolic state and transcription.

The goal of my lab is to explore how the metabolic state of a given cell, tissue or organism directly impacts the function of RNA polymerase in its job transcribing specific genes. Projects in the lab will: 1) Define the function for the novel metabolite RNA caps, be it as a link between metabolism and transcriptional or post-transcriptional gene regulation or a more direct role in the function of capped transcripts; 2) answer fundamental questions about transcription both in bacterial systems and in eukaryotic mitochondria such as how metabolite and nucleotide levels under different metabolic states directly affect gene expression at the level of transcription; 3) use these new insights to inform our understanding of how bacteria survive in diverse environments as well as apply the work done in mitochondria to cancer and other diseases that affect mitochondrial function.

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