Science for All Seasons gives you a chance to explore hot topics in genomics with leading experts from the Broad Institute. Find out what key advances, new technologies, and the latest findings mean for you in this free and open lecture series.
Harnessing Evolution to Solve Problems in Biotechnology and Therapeutics Science
Biological evolution has solved many challenging molecular problems with breathtaking effectiveness. Researchers have begun to harness the remarkable power of evolution to address problems of their own choosing, rather than of nature’s choosing. In this lecture, Liu will describe the development and first applications of phageassisted continuous evolution (PACE), a method that enables proteins to evolve continuously in the laboratory for the first time, accelerating the speed of laboratory evolution ~100fold. The Liu group has used PACE to rapidly evolve a wide variety of proteins with the potential to serve as novel therapeutic agents, as well as to study the reproducibility and path dependence of evolution over thousands of generations in a practical time frame. Liu will also describe a recent effort to use PACE to address a major problem facing worldwide agricultural productivity: the rise of insects resistant to a widely used protein insecticide.
David R. Liu is the Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare, vice chair of the faculty at the Broad Institute of MIT and Harvard, the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard University, and a Howard Hughes Medical Institute (HHMI) investigator. Liu’s research integrates chemistry and evolution to illuminate biology and enable next-generation therapeutics. His major research interests include the engineering, evolution, and in vivo delivery of genome editing proteins such as base editors to study and treat genetic diseases; the evolution of proteins with novel therapeutic potential using phage-assisted continuous evolution (PACE); and the discovery of bioactive synthetic small molecules and synthetic polymers using DNA-templated organic synthesis and DNA-encoded libraries. Base editing — the first general method to perform precision gene editing without double-stranded breaks, and a Science 2017 Breakthrough of the Year finalist — as well as prime editing, PACE, and DNA-templated synthesis are four examples of technologies pioneered in his laboratory. These technologies are used by thousands of laboratories around the world and have enabled the study and potential treatment of many genetic diseases.
Liu graduated first in his class at Harvard College in 1994. During his doctoral research at U. C. Berkeley, Liu initiated the first general effort to expand the genetic code in living cells. He earned his Ph.D. in 1999 and became assistant professor of chemistry and chemical biology at Harvard University in the same year. He was promoted to associate professor in 2003 and to full professor in 2005. Liu became a Howard Hughes Medical Institute investigator in 2005 and joined the JASONs, academic science advisors to the US government, in 2009. In 2016 he became a core institute member and vice-chair of the faculty at the Broad Institute of MIT and Harvard, and director of the Chemical Biology and Therapeutics Science Program.
Liu has been elected to the US National Academy of Sciences, the US National Academy of Medicine, and the American Association for the Advancement of Science. He is the 2022 King Faisal Prize Laureate in Medicine. He has earned several university-wide distinctions for teaching at Harvard, including the Joseph R. Levenson Memorial Teaching Prize, the Roslyn Abramson Award, and a Harvard College Professorship. Liu has published more than 220 papers and is the inventor on more than 85 issued US patents. His research accomplishments have earned distinctions including the Ronald Breslow Award for Biomimetic Chemistry, the American Chemical Society David Perlman Award, ACS Chemical Biology Award, the American Chemical Society Pure Chemistry Award, the Arthur Cope Young Scholar Award, the NIH Marshall Nirenberg Lecturer, and awards from the Sloan Foundation, Beckman Foundation, NSF CAREER Program, and Searle Scholars Program. In 2016 and 2020 he was named one of the Top 20 Translational Researchers in the world by Nature Biotechnology, and was named one of Nature’s 10 researchers in the world and to the Foreign Policy Leading Global Thinkers in 2017. He is the founder or co-founder of several biotechnology and therapeutics companies, including Beam Therapeutics, Prime Medicine, Editas Medicine, Pairwise Plants, Exo Therapeutics, Chroma Medicine, and Resonance Medicine.
Medical Interpretation of Human Genomes
With the plummeting cost of sequencing, genetic data is becoming increasingly available for use in the diagnosis, treatment and prediction of disease. Ensuring the successful use of genomics in medicine will require the community to come together to share data and contribute to the collective curation of that data for clinical and research use. This talk will focus on national and international efforts to develop improved standards and resources to support genomic medicine.
Heidi Rehm, a human geneticist and genomic medicine researcher, is co-director of the Program in Medical and Population Genetics and an institute member at the Broad Institute. She is the chief genomics officer in the Department of Medicine at Massachusetts General Hospital (MGH), working to integrate genomics into medical practice with standardized approaches. She is also a professor of pathology at Harvard Medical School and faculty member of the Center for Genomic Medicine at MGH.
As a board-certified laboratory geneticist and medical director of the Clinical Research Sequencing Platform, she is guiding genomic testing for clinical and clinical research use. She is a leader in defining standards for the interpretation of sequence variants and a principal investigator of a major NIH-funded effort called ClinGen (Clinical Genome Resource), providing free and publicly accessible resources to support the interpretation of genes and variants.
Rehm also co-leads the Broad Center for Mendelian Genomics with Anne O’Donnell-Luria focused on discovering novel rare disease genes and co-leads the Matchmaker Exchange to aid in gene discovery. She is a strong advocate and pioneer of open science and data sharing, working to extend these approaches through her role as a vice chair of the Global Alliance for Genomics and Health. Rehm is also a principal investigator of the Broad-LMM-Color All of Us Genome Center, supporting the sequencing and return of results to a cohort of one million individuals in the U.S. and co-leading gnomAD, the Genome Aggregation Database.
Rehm is a board member of the American College of Medical Genetics and Genomics and the National Library of Medicine. She serves as an editor of the Cold Spring Harbor Molecular Case Studies journal and as an associate editor of the American Journal of Human Genetics. Among Rehm's honors are the BWH Physician Recognition Award for Clinical Innovation and the Boston Business Journal's 40 Under 40 Award for Civic Leadership. She was also a member of the team that won the 2012 CLARITY Challenge run by Boston Children’s Hospital and the 2013 Bio-IT World Editors’ Prize for the GeneInsight software system.
Rehm received her B.A. degree in molecular biology and biochemistry from Middlebury College before earning her M.S. in biomedical science from Harvard Medical School and Ph.D. in genetics from Harvard University. She completed her post-doctoral training with David Corey in neurobiology and a fellowship in clinical molecular genetics at Harvard Medical School.
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Synthetic Biology: Redesigning Life
Description: Synthetic biology is bringing together engineers, physicists, and biologists to construct biological circuits out of proteins, genes, and other bits of DNA, and to use these circuits to rewire and reprogram organisms. These re-engineered organisms are going to change our lives in the coming years, leading to cheaper drugs, rapid diagnostic tests, and synthetic probiotics to treat infections and a range of complex diseases. In this talk, we highlight recent efforts to create synthetic gene networks and programmable cells and discuss a variety of synthetic biology applications in biotechnology and biomedicine.
Jim Collins is the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT, as well as a member of the Harvard-MIT Health Sciences & Technology faculty. He is also a core founding faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University and an Institute member of the Broad Institute of MIT and Harvard.
His research group works in synthetic biology and systems biology, with a particular focus on using network biology approaches to study antibiotic action, bacterial defense mechanisms, and the emergence of resistance. Collins's patented technologies have been licensed by over 25 biotech, pharmaceutical, and medical device companies, and he has helped to launch a number of companies, including Sample6 Technologies, Synlogic, and EnBiotix.
He has received numerous awards and honors, including a Rhodes Scholarship, a MacArthur "Genius" Award, an NIH Director's Pioneer Award, and several teaching awards. Collins is an elected member of the National Academy of Sciences, the National Academy of Engineering, and the National Academy of Medicine,as well as the American Academy of Arts & Sciences and the National Academy of Inventors.
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