David L. Weaver Endowed Lecture

Dr. Weaver made significant contributions to the understanding of protein folding. He was impressed with the research and faculty at the UC Davis Genome Center, where he was planning to spend his sabbatical year 2006-2007. Dr. Weaver focused his early research on high-energy physics, studying photon production and elementary particles. He spent a year and a half as a NATO Fellow at the European Center for Nuclear Research (CERN), in Geneva, Switzerland, where he met his wife, Elena Weaver. After his time at CERN, he returned to Tufts and began to think about how he could apply his physics background to problems in biology. While he continued to make significant contributions in high-energy physics, for which he received tenure at Tufts in 1969, Dr. Weaver's interests continued to shift towards some of the key unsolved problems in biology. At the University of Rome, Italy, as a visiting CNN Fellow at the Frascati National Laboratory, he became more and more interested in applying his mathematical skills to gain a better understanding of molecular dynamics. He visited Dr. Martin Karplus at Harvard during a sabbatical in 1972, and they began a collaboration that culminated in a paper about a then theoretical diffusion-collision model for protein folding (Nature, 1976). The Diffusion-Collision Model was ahead of its time because the data needed to test it were not available when it was published in 1976. But by the mid-1990s experimental studies had shown that the model did indeed describe the folding mechanism of many proteins. The field has been completely transformed in recent years because of its assumed importance for understanding the large number of protein sequences available from genome projects, says Karplus, and because of the realization that misfolding can lead to a wide range of human diseases. Dr. Weaver received grants from NASA, NATO, Bruker Optics, and the NIH to establish computer facilities at Tufts where he continued to work with students, Dr. Karplus, and other collaborators to improve his understanding of important biophysical problems. He was a regular visitor at labs overseas and in the United States, and he authored or co-authored a number of significant scientific publications. He held degrees in Chemistry from Rensselaer Polytechnic Institute and in Physical Chemistry from Iowa State University. A Fellow of the American Physical Society, Dr. Weaver also served as the chair of the Tufts Department of Physics and Astronomy from 1989 to 2002. He was born in Albany, NY, on April 18th, 1937. David Weaver possessed an easy manner, a sense of fairness, curiosity and an enjoyment of life that was evident in his teaching and relations with colleagues. All who knew him will miss his kind and cheerful humor, his smile, and his generous spirit.

Upcoming Lecture 

April 2nd, 2025

 3-4 pm

Genome and Biomedical Sciences Facility, Auditorium

Professor AndreJ Sali, 

Department of Bioengineering and Therapeutic Sciences
Department of Pharmaceutical Chemistry
California Institute for Quantitative Biosciences
University of California, San Francisco

Research Collaboratory for Structural Bioinformatics Protein Data Bank, Department of Bioengineering and Therapeutic Sciences, Quantitative Biosciences Institute (QBI), and Department of Pharmaceutical Chemistry, University of California, San Francisco. From Integrative Structural Biology to Cell Biology.

Integrative modeling is an increasingly important tool in structural biology, providing structures by combining data from varied experimental methods and prior information. As a result, molecular architectures of large, heterogeneous, and dynamic systems, such as the ~52 MDa Nuclear Pore Complex, can be mapped with useful accuracy, precision, and completeness. Key challenges in improving integrative modeling include expanding model representations, increasing the variety of input data and prior information, quantifying a match between input information and a model in a Bayesian fashion, inventing more efficient structural sampling, as well as developing better model assessment, analysis, and visualization. In addition, two community-level challenges in integrative modeling are being addressed under the auspices of the Worldwide Protein Data Bank (wwPDB). First, the impact of integrative structures is maximized by PDB-Dev, a prototype wwPDB repository for archiving, validating, visualizing, and disseminating integrative structures. Second, the scope of structural biology is expanded by linking the wwPDB resource for integrative structures with archives of data that have not been generally used for structure determination but are increasingly important for computing integrative structures, such as data from various types of mass spectrometry, spectroscopy, optical microscopy, proteomics, and genetics. To address the largest of modeling problems, a type of integrative modeling called metamodeling is being developed; metamodeling combines different types of input models as opposed to different types of data to compute an output model. Collectively, these developments will facilitate the structural biology mindset in cell biology and underpin spatiotemporal mapping of the entire cell.

Previous Lectures