Member, Whitehead Institute

David Bartel

The Bartel Lab studies how cells regulate gene expression by changing the stability or translation of mRNAs

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A man in a blue sweater stands against a white wall.

455 Main Street
Cambridge, MA 02139
United States

617.258.7778
resteghini@wi.mit.edu

Achievements & Honors

Co-discovered the abundance of microRNAs and helped define this class of small regulatory RNAs
Developed the methodology to accurately predict the regulatory targets of microRNAs in both plants and animals
Ascertained molecular consequences and biological roles of microRNA regulation, including how a microRNA helps prevent human cancer
Discovered heterochromatic siRNAs, which direct DNA silencing, and other types of small regulatory RNAs
Created ribozyme (RNA enzyme) that synthesizes pieces of RNA, bolstering the "RNA world" theory
Co-founder, Alnylam Pharmaceuticals
AAAS Newcomb Cleveland Prize (2002)
NAS Molecular Biology Award (2005)
Institut de France Louis-D. Prize (2005)
Elected member of the National Academy of Sciences (2011)

Affiliations

Member, Whitehead Institute
Professor of Biology, MIT
Investigator of the Howard Hughes Medical Institute

Question

Why are some mRNAs much more long-lived than others or translated much better than others, and how do these differences in post-transcriptional gene regulation influence cellular function and development?  

 

Approach

mRNAs from different genes can have very different rates of decay or very different efficiencies of translation, and these differences can have profound effects on the amount of each protein produced by each cell. The Bartel lab uses innovative high-throughput biochemical and molecular analyses, together with computational and evolutionary approaches to gain initial insight into these gene-regulatory processes and generate new hypotheses. They then follow up on these insights with genetic, molecular, and in-depth biochemical analyses designed to elucidate molecular mechanisms.  

Bartel has a longstanding interest in microRNAs, which are short RNAs that interact with sites in mRNAs to direct the destabilization or translational repression of these targeted transcripts. The Bartel lab helped to define this class of small regulatory RNAs, their mRNA targets, and the molecular consequences of their action. For example, they and their collaborators showed that most human mRNAs are regulated by microRNAs. The lab is currently generating millions of affinity measurements that are revealing unanticipated differences between different microRNAs and providing information required to improve predictions of microRNA regulatory interactions. The lab is also turning its attention from how microRNAs are produced by the cell to how certain microRNAs are destroyed in a process that helps to shape the levels of different microRNAs in different cell types. This process is highjacked by some viruses, which use it to eliminate microRNAs that would otherwise impede viral replication.

In other experiments, the lab studies mRNAs, with emphasis on how mRNA structure, mRNA untranslated regions, and mRNA poly(A) tails recruit and mediate regulatory phenomena.  For example, they are learning why in early embryos mRNAs with shorter tails are translated less efficiently than those with longer tails, whereas later in development mRNAs with shorter tails are no longer less efficiently translated and instead are more rapidly degraded. The lab is also studying a recently discovered regulatory function for excised introns, which are RNA regions that are normally removed from mRNAs and then rapidly destroyed.
 

Bio

Bartel earned his bachelor’s degree in biology from Goshen College in 1982 and his Ph.D. degree in Virology from Harvard University in 1993, under the mentorship of Jack W. Szostak. Bartel joined Whitehead Institute in 1994 as a Whitehead Fellow. In 1996, he was appointed an Associate Member of Whitehead and assistant professor of biology at MIT. Bartel is now a Howard Hughes Medical Institute Investigator, a Member at Whitehead, and professor at MIT.

 

Selected publications

Charlie Y Shi, Elena R Kingston, Benjamin Kleaveland, Daniel H Lin, Michael W Stubna, David P Bartel
Sean E McGeary, Kathy S Lin, Charlie Y Shi, Thy M Pham, Namita Bisaria, Gina M Kelley, David P Bartel
Jeffrey T Morgan, Gerald R Fink, David P Bartel