- Professor of Molecular and Cellular Biology and of Applied Mathematics
- Investigator, Howard Hughes Medical Institute
We are interested in deciphering the evolutionary history of life by comparative analysis of genome sequences. We develop computational algorithms and software tools for genome sequence analysis, including the HMMER and Infernal software packages for identifying distant homologs of biological sequence families. We rely on Bayesian probabilistic inference approaches, including hidden Markov models (stochastic regular grammars) for primary structure analysis of proteins and DNA, and stochastic context-free grammars for RNA secondary structure and sequence analysis.
We have a special interest in RNA. The "ancient RNA world" hypothesis says that an ecosphere of RNA-based life preceded protein/DNA based life. Some RNA genes that we see today are thought to be ancient relics of the RNA world. By studying modern RNAs, we may learn something about the origins of life. While doing this, we and others have also been finding that the RNA World model is pessimistic in a sense: far from being a few scattered relics, RNAs are in widespread use in modern organisms in a variety of roles. We have argued for a "modern RNA world" hypothesis, that many of the RNAs we see today are modern inventions, highly adapted to regulatory roles in complex organisms.
Most recently, our laboratory has begun working on one of the greatest mysteries in biology: how a relatively small genome manages to specify biological complexity, especially something as complex as what we see in the neural circuits of a brain. This is an area where molecular evolutionary biology still largely lacks quantitative language for asking precise questions. As one way forward in this difficult frontier, we collaborate with neuroscientists working on the molecular regulatory specification of neural cell types in fly, worm, and mouse.
Positions & Employment
1995-2000 Assistant Professor, Dept. of Genetics, Washington University School of Medicine
2000-2001 Alvin Goldfarb Professor of Computational Biology, Washington U. School of Medicine
2004 Visiting Senior Fellow, Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute
2000-2007 Adjunct Professor, Dept. of Biomedical Engineering, Washington U. (by courtesy)
2000-2007 Adjunct Professor, Dept. of Computer Science, Washington U. (by courtesy)
2000-2007 Associate Professor, Department of Genetics, Washington U. School of Medicine
2000-2006 Investigator, Howard Hughes Medical Institute
2001-2007 Alvin Goldfarb Distinguished Professor of Computational Biology, Washington University School of Medicine
2006-2015 Group leader, HHMI Janelia Research Campus
1986 Bachelor of Science degree with Honors
1988-1991 National Science Foundation Graduate Student Fellowship
1991 U. of Colorado Graduate Student Research and Creative Work Award
1992-1994 Postdoctoral Fellowship, Human Frontier Science Program
1994-1995 Postdoctoral Fellowship, National Institutes of Health
1997 Eli Lilly Biochemistry Academic Contacts Committee award
2002 Fellow of the Academy of Science of St. Louis
2007 Benjamin Franklin Award for Open Access in the Life Sciences
2014 Fellow of the American Association for the Advancement of Science (AAAS)
US Patent 7250556 Transposable elements in rice and methods of use (2007).