Genomics - Weekly Calendar

Jeff Gore, MIT, Anticipating sudden transitions in biological populations: Cooperation, cheating, and collapse
http://web.mit.edu/physics/people/faculty/gore_jeff.html

Anticipating sudden transitions in biological populations: Cooperation, cheating, and collapse

Natural populations can suffer catastrophic collapse in response to small changes in environmental conditions, and recovery after such a collapse can be exceedingly difficult. We have used laboratory microbial ecosystems to study early warning signals of impending population collapse. Yeast cooperatively breakdown the sugar sucrose, meaning that below a critical size the population cannot sustain itself. We have demonstrated experimentally that changes in the fluctuations of the population size can serve as an early warning signal that the population is close to collapse. The cooperative nature of yeast growth on sucrose suggests that the population may be susceptible to cheater cells, which do not contribute to the public good and instead merely take advantage of the cooperative cells. We confirm this possibility experimentally and explore how such social parasitism can lead to population extinction.
Carl Icahn Lab 101  ·  4:15 p.m.– 5:15 p.m.

Nicholas Ingolia, Carnegie Institution, Global profiling of translation initiation and protein synthesis
http://www.ingolia-lab.org/

Proteins are the ultimate functional products of most genes, and protein synthesis is a key point of regulation in determining the amount of protein that a cell produces. Translational regulation can also control the production of different protein isoforms from the same transcript and can impact the folding and localization of these protein products. Our appreciation of the full biological impact of translational control has been limited by the difficulty of measuring in vivo translation. We have addressed this challenge by developing ribosome profiling as a technique for monitoring gene expression, globally, at the level of actual protein synthesis. We identified a broad program of translational regulation linked to cell growth, acting in mouse embryonic stem cells as well as in cancer cells, downstream of the mammalian target of rapamycin (mTOR) kinase. Ribosome profiling also revealed unexpected complexity in translation initiation, which likely represents a mechanism controlling protein synthesis. In a few well-studied genes, alternative upstream translation start sites provide transcript-specific control of protein synthesis. Our results suggest that this mechanism could affect many genes, including key regulators of proliferation and pluripotency in ES cells. Alternate sites of translation initiation also yield alternate protein isoforms with distinct and even opposing functions. Ribosome profiling promises to further expand our understanding of the proteins synthesized by the cell and the regulation of their expression.
Carl Icahn Lab 101  ·  3:30 p.m.– 4:30 p.m.

Gloria Brar, UCSF, Using high-resolution translation measurements to define meiotic cellular remodeling and redefine genome coding
http://weissmanlab.ucsf.edu/people/people.html

Meiosis is a complex and well-conserved program of cellular differentiation. I performed genome-wide measurements of mRNA abundances and new translation using ribosome profiling through yeast meiosis to better understand the molecular basis for the full cellular restructuring that accompanies meiotic chromosome segregation. This global view of translation through a developmental process revealed great complexity to the protein complement of these differentiating cells, both in the number and the structure of expressed genes. Nearly every gene in the yeast genome was translated in meiotic cells in a strongly stage-specific manner, including disparate and regulated induction of conserved canonical stress pathways such as the Unfolded Protein Response. Translational regulation contributed broadly to this temporal control of protein synthesis timing through several distinct mechanisms. Additionally, meiotic translation of thousands of novel short ORFs was observed, expanding our view of what constitutes a coding region even in the most well annotated eukaryotic genome.
Lewis Thomas Lab 003  ·  9:30 a.m.–10:30 p.m.