| 293 | Jeremy Bird, Ph.D. | <p>​​Assistant Professor<br></p> | 302-831-1332 | | jgbird@udel.edu | 324 Wolf Hall | | | <p></p><ul><li>​BS - Loyola University in Maryland</li><li>PhD - Cornell University</li><li>Post-doctoral - The Waksman Institute of Microbiology, Rutgers University<br></li></ul><p></p> | | <p>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. </p><p>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.</p><p>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.<br></p> | <ol><li>Using next generation sequencing to elucidate the mechanism of transcription by mitochondrial polymerases</li><li>Understanding how substrate availability (NTPs, NAD(H), etc.) affects transcription as the first step in gene expression</li><li>Determining the functional roles for RNA metabolite caps such as NAD(H) and dpCoA</li></ol> | | <p>Full list of publications on <a href="https://scholar.google.com/citations?user=LvNTfmAAAAAJ&hl=en&oi=sra">Google Scholar</a>.<br></p><p><strong>​Bird JG*</strong>, Basu U*, Kuster D, Grudzien-Nogalska E, Kiledjian M, Temiakov D, Patel SS, Ebright RH, Nickels BE. Mitochondrial RNA capping: highly efficient 5'-RNA capping with NAD+ and NADH by yeast and human mitochondrial RNA polymerase. eLife (2018). 7:e42179. </p><p>Grudzien-Nogalska E, <strong>Bird JG</strong>, Nickels B, Kiledjian M. 'NAD-capQ' Detection and Quantitation of NAD caps. RNA (2018). doi: 10.1261.</p><p>Vvedenskaya IO*, <strong>Bird JG</strong>*, Zhang Y*, Zhang Y, Jiao X, Krásný L, Kiledjian M, Taylor DM, Ebright RH, Nickels BE. CapZyme-seq comprehensively defines promoter-sequence determinants for 5′ capping with NAD. Mol Cell (2018). 70(3):553-564</p><p><strong>Bird JG</strong>, Nickels BE, Ebright RH. RNA capping by transcription initiation with non-canonical initiating nucleotides (NCINs): Determination of relative efficiencies of transcription initiation with NCINs and NTPs. Bio-Protocol (2017). 7(12).</p><p>Jiao X, Doamekpor S, <strong>Bird JG</strong>, Nickels BE, Hart RP, Tong L, Kiledjian M. 5′ end nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding. Cell (2017).168(6):1015-1027.</p><p><strong>Bird JG</strong>, Zhang Y, Tian Y, Panova N, BarvÃk I, Greene L, Liu M, Buckley B, Krásný L, Lee JK, Kaplan CD, Ebright RH, Nickels BE. The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA. Nature (2016). 535: 444-447. </p><p>Winkelman JT, Vvedenskaya IO, Zhang Y, <strong>Bird JG</strong>, Taylor DM, Gourse RL, Ebright RH, Nickels BE. Multiplexed protein-DNA cross-linking: Scrunching in transcription start site selection. Science (2016). 351(6277):1090-3.</p><p><strong>Bird JG</strong>,<strong> </strong>Strobel EJ,<strong> </strong>Roberts JW. A universal transcription pause sequence is an element of initiation factor s-70 dependent pausing. Nucleic Acid Research (2016) 44(14):6732-6740.</p><p>Rueggeberg KG, Toba FA, <strong>Bird JG</strong>, Franck N, Thompson MG, Hay AG. The lysis cassette of DLP12 defective prophage is regulated by RpoE. Microbiology (2015) 161(8):1683-93.</p><p>Vvedenskaya IO*, Vahedian-Movahed H*, <strong>Bird JG</strong><strong>*</strong>, Knoblauch JG, Goldman SR, Zhang Y, Ebright RH, Nickels BE. Interactions between RNA polymerase and the "core recognition element" counteract pausing. Science (2014). 344 (6189): 1285-1289.</p><p><strong>Bird JG</strong>, Sharma S, Roshwalb SC., Hoskins, J.R., Wickner, S. Functional Analysis of CbpA, a DnaJ homolog and nucleoid associated DNA binding protein. J. Biol. Chem. (2006) 281: 34349-34356.</p><p>Sharma S, Sathyanarayana BK, <strong>Bird JG</strong>, Hoskins JR, Lee BK, Wickner S. Plasmid P1 RepA is homologous to the F Plasmid RepE class of initiators. J. Biol. Chem. (2004) 279:6027-34.</p><br> | | | <img alt="Jeremy Bird, Ph.D." src="/content-sub-site/PublishingImages/people/jgbird/jgbird-180x240.jpg" style="BORDER:0px solid;" /> | |
