New Frontiers in Proteomics – Proteoforms, Proteoform Families, and the Human Proteoform Project

Description:
Proteins are the primary effectors of function in biology, and thus complete knowledge of their structure and behavior is needed to decipher function. However the richness of protein structure and function goes far beyond the linear amino acid sequence dictated by the genetic code. Multigene families, alternative splicing, coding polymorphisms, and post-translational modifications, work together to create a rich variety of proteoforms, whose chemical diversity is the foundation of the biological complexes and networks that control biology. Here, the term “proteoforms” refers to the specific molecular forms in which proteins are present in biological systems; only direct analysis of the intact proteoforms themselves can reveal their structures, dynamics, and localizations in biological systems. Devising new strategies and approaches that are able to comprehensively and quantitatively reveal the full breadth of the proteome at the proteoform level is a “grand challenge” to the scientific community. In this presentation I will provide an overview of this interesting problem, along with a variety of new tools and approaches that we and others are developing to address it. A key integrating concept is the “proteoform family”, the set of all proteoforms that derive from a given gene. The description of the proteome of a given sample of interest may thus be considered as a set of proteoform families, one for each gene in the genome. Identifying and quantifying the members of each proteoform family comprises a new way of conceptualizing proteome analysis in complex systems. Developing the technology to accomplish this, building a comprehensive atlas of proteoforms present in human systems, and eventually deciphering the functional roles they play in normal and disease biology, comprise central elements in the quest to understand human biology.

Speaker: Lloyd Smith - University of Wisconsin - Madison
Lloyd M. Smith is the W. L. Hubbell Professor of Chemistry at the University of Wisconsin-Madison, where he has been since 1988. He received an A.B. degree in Biochemistry from the University of California at Berkeley (1977) and a Ph.D. in Biophysics from Stanford University (1981). In 1982 he moved to the California Institute of Technology, where he invented the first fluorescence-based automated DNA sequencing instrument. He has been named one of Science Digest's Top 100 Innovators and has received the Presidential Young Investigator Award, Eli Lilly Analytical Chemistry Award, Association of Biomolecular Resource Facilities Award for the development of automated DNA sequencing, American Chemical Society Award in Chemical Instrumentation, and the Pittsburgh Analytical Chemistry Award. He is an author of over 300 scientific papers, with an H-index of 85, and inventor on 40 issued U.S. patents.