MicroRNAs, poly(A) tails, and a developmental switch in the nature of translational control
David Bartel, HHMI/MIT/Whitehead Institute, 9 Cambridge Center, Cambridge, MA
We have been using molecular and computational approaches to find regulatory RNAs, identify the messages that they regulate, and then investigate molecular consequences of these regulatory interactions as well as their functions during development, oncogenesis, and other biological processes. This talk will describe our current understanding of microRNAs, our progress in predicting their targets, and how our measurements of their regulatory effects has revealed an unexpected developmental switch in the nature of mRNA translational control. During this switch, the coupling between poly(A)-tail length and translational efficiency, known to occur in oocytes and early embryos, rapidly disappears, such that translation in later embryos and most adult tissues is no longer dependent on poly(A)-tail length. Implications for understanding microRNA effects as well as gene regulation more generally will be discussed.
Genomic Studies of Bacterial Pathogen Evolution and Drug Resistance
Ashlee Earl, Group Leader, Bacterial Genomics,Genome Sequencing & Analysis Program,The Broad Institute of MIT & Harvard, Cambridge, MA
New sequencing technologies are providing extraordinary opportunities to tackle longstanding and emerging challenges in infectious disease. Capitalizing on these technologies requires thoughtful study design, access to appropriate samples, metadata, and development of suitable analytical approaches. The emergence of multidrug resistant strains of pathogens has become a leading public health concern. To address this concern, we have developed new approaches and tools to examine drug resistant Mycobacterium tuberculosis, and to study the emergence of multidrug resistant strains of enterococci as leading causes of hospital acquired infection. These tools include new algorithms for identifying sequence polymorphisms and adapting existing algorithms for the very large data sets that are now being produced by next generation sequencing. In close partnership with our collaborators, we sequenced and applied these tools to the analysis of genomes from large sets of well-characterized strains of mycobacteria and enterococci. Among our findings with M. tuberculosis, we identified harbinger mutations of multidrug resistance that may inform new strategies for preempting emergence of successive resistance. With enterococci, we have found that vancomycin resistant Enterococcus faecium evolved as the result of anthropogenic forces over the past 5,000 years, and that there is substantial diversity in gene content within this genus. I will discuss our findings as well as the development of analytical approaches that take into account the unique features and distinct evolutionary history of each species’ genome.