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, director of the Merkin Institute of Transformative Technologies in Healthcare, and vice chair of the faculty at the Broad Institute of Harvard and MIT; a professor of chemistry and chemical biology 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 (named one of four 2017 Breakthrough of the Year finalists by Science), PACE, and DNA-templated synthesis are three examples of technologies pioneered in his laboratory.
Liu graduated first in his class at Harvard in 1994. He performed organic and bioorganic chemistry research on sterol biosynthesis under Professor E. J. Corey’s guidance as an undergraduate. During his Ph.D. research with Professor Peter Schultz 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 U.S. government, in 2009.
Liu 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 160 papers and is the inventor on more than 60 issued U.S. patents. His research accomplishments have earned distinctions including the Ronald Breslow Award for Biomimetic Chemistry, the American Chemical Society Pure Chemistry Award, the Arthur C. Cope Young Scholar Award, and awards from the Sloan Foundation, Beckman Foundation, NSF CAREER Program, and Searle Scholars Program. In 2016 he was named one of the top 20 translational researchers in the world by Nature Biotechnology, and in 2017 was named to the Nature’s 10 researchers in world and to the Foreign Policy Leading Global Thinkers. He is the scientific founder or co-founder of six biotechnology and therapeutics companies, including Editas Medicine, Pairwise Plants, and Beam Therapeutics.
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 medical director of the Clinical Research Sequencing Platform and an institute member at the Broad Institute. She is chief genomics officer in the Department of Medicine at Massachusetts General Hospital (MGH). She is also a professor of pathology at MGH, Brigham and Women's Hospital (BWH) and Harvard Medical School. She is a board-certified geneticist and 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 Daniel MacArthur 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 on the steering committee of the Global Alliance for Genomics and Health. Rehm is also a co-investigator of the BabySeq Project exploring the clinical use of genomic sequencing as an adjunct to newborn screening; principal investigator in the eMERGE consortium supporting genomic discovery and genomic medicine implementation; and a principal investigator on a project to develop the Informatics for Integrating Biology and the Bedside (i2b2) center into a health innovation platform for clinical decision support.
In 2001, Rehm began building the Laboratory for Molecular Medicine (LMM) within the Harvard-Partners Center for Genetics and Genomics. Now a part of Partners HealthCare Personalized Medicine, the LMM focuses on the rapid translation of new genetic discoveries into clinical tests and brings novel technologies and software systems into clinical use to support the integration of genetics into medicine. The laboratory, which Rehm directed until 2018, has been a leader in translational medicine, and offers exome and genome sequencing services for both clinical diagnostics and to support genomic medicine research projects.
Rehm is involved in defining standards for the use of next generation sequencing in clinical diagnostics and the interpretation of sequence variants through her committee roles at the American College of Medical Genetics and Genomics. She serves as a council member of the Human Genome Organization, Human Genome Variation Society, and Human Variome Project. 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 teams 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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