CCB Seminar: Michael Wigler

Date & Time

Title: Biological thought experiments and thecomputations they spawn

Abstract: Iwill talk about aspirations that bridge biology and computation. The first is determiningthe landscape of genetic contribution to autism. The second relates uncoveringpatterns of hominid mixing from present day sequence information. The third is speculations on evolution ofbiological systems.

(1) The Simons Foundation (SF) hascreated a rich resource for studying the genetics of autism, adevelopmental-neurological disorder, in the form of quad family whole genomesequence data. Although not easy, from enough of such data one could inprinciple determine the frequency with which new mutation and transmittedvariants contribute to autism. I will sketch out the genetic landscape in lowresolution now, with a discussion of how sharp it can become in the future. In particular, there are remaining challenges,paradoxes and enigmas. The path forward is largely (but not exclusively)computational and I will describe the kind of progress we can expect, and thekind of additional data needed.

(2) Quad family sequence data alsoprovide a possible portal into the human past, in the form of haplo-sequences.While not yielding a precise record of past genetic events, we may be able tosee into the past. For example, we might be able to determine if rates ofmutation have changed over recent human history, and we might see evidence oflarge scale intermixing of formerly isolated populations.

(3) Ant behavior can be modeled withfairly simple “algorithms”. We are beginning to investigate if we can implementthese as spatially-local algorithms that have rapid compute times andscalability. Thinking about the simplest ways to do this leads to speculationon genetic decay, evolution, tribalism, wars, and the molecular origins of self-recognition.I suspect we may discover the external conditions that drive species to undergoa phase transition to eusocial organization.

About the Speaker

Dr. Michael Wigler received his Ph.D. in Microbiology in 1978 from Columbia University.  Upon completion of the doctoral degree, he became Head of the Mammalian Cell Genetics Section at Cold Spring Harbor Laboratory, where is now Professor.  Together with Axel and Silverstein at Columbia, he discovered co-transformation, a technique still used for engineering mammalian cells to produce medicinally useful proteins. His team was the first to isolate a mammalian gene using gene transfer techniques and among the first to identify a human oncogene by this means.  His laboratory discovered the involvement of three members of the RAS family in human cancer; demonstrated the inheritance of DNA methylation patterns; pioneered the use of yeast as a model to explore more complex organisms, leading to an understanding of the RAS signaling pathway; co-invented (with Clark Still of Columbia University) encoded combinatorial synthesis, which has accelerated the discovery of new drug candidates; together with Nikolai Lisitsyn invented RDA, a method for comparative genome analysis that led to the discovery of the PTEN tumor suppressor (with Ramon Parsons of Columbia University) and the Kaposi’s sarcoma virus (by others at Columbia University); developed representational genomic approaches that are used widely in genotyping; and applied array hybridization methods and representational analysis to genomic analysis (ROMA). Dr. Wigler’s research is presently focused on the genomics of cancer and genetic disorders. Together with Jim Hicks and Nick Navin his laboratory demonstrated the feasibility of single cell sequencing for genomic analysis and expects this work will eventually improve the targeting of cancer treatments and lead to early and less invasive tests for cancer. His studies in human genetics led to the discovery of a vast unsuspected source of genetic variability known as copy number variation (CNV), and to the hypothesis that spontaneous mutation is a major cause of autism. Dr. Wigler was elected to the National Academy of Sciences in 1989 and to the American Academy of Arts & Sciences in 1999, and is the recipient of many awards, including the Double Helix Medal in 2007.

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