ADI) Program Supports Early-Stage Research with the Potential to Reinvent Entire Fields

FACT SHEET Allen Distinguished Investigators The Allen Distinguished Investigator (ADI) program supports early-stage research with the potential to reinvent entire fields. Allen Distinguished Investigators are passionate thought leaders, explorers and innovators who seek world-changing breakthroughs. With grants typically between $1 million and $1.5 million each, the scientists will receive support to produce new directions in their respective fields. The new ADI recipients are: Ethan Bier, Ph.D., University of California, San Diego, “Biological Innovation and Active Genetics” Award amount: $1.5 million Project description: A major unsolved mystery in evolutionary developmental biology is how biological innovation happens: where do new body forms come from? Using pioneering technology known as active genetics to produce large genetic modifications, Bier will seek to uncover the design principles used in evolution to make large-scale physical changes across species. The practical applications of this work promise to guide novel synthetic biology designs that could revolutionize medicine, agriculture and care of the environment. Investigator bio: Ethan Bier is a professor in the section of Cell and Developmental Biology at UC San Diego. During the past 25 years at UCSD Dr. Bier has studied how secreted morphogen proteins subdivide the dorsal- ventral axis of the fruit fly embryo into neural versus epidermal regions and how such processes result in the formation of sharp boundaries during development of the wing. These are among the most conserved evolutionary processes. Dr. Bier has also used fruit flies to study mechanisms of human disease, focusing on understanding the mechanisms by which bacterial toxins contribute to breaching host barriers. Thus, two toxins produced by anthrax bacteria trigger potentially fatal vascular leakage while cholera toxin leads to breakdown of the intestinal barrier leading to acute life-threatening diarrhea. His findings that these toxins disrupt transport of proteins to cell junctions required for barrier integrity suggest possible therapeutic approaches to combat anthrax and cholera as well as a variety of inflammatory diseases such as IBD and asthma, which also involve barrier dysfunction. Dr. Bier recently has made a discovery allows the conversion of heterozygous mutants to homozygotes that promises to revolutionize control of vector borne diseases (e.g., malaria) and pests, genetic manipulation of organisms for medical and agricultural research, and treatment of cancer, HIV, and other maladies. Dr. Bier graduated Phi Beta Kappa as a Regents Scholar from UCSD in 1978 with degrees in Biology and Mathematics. He received his Ph.D. from Harvard Medical School on regulation of immune genes in Dr. Allan Maxam’s laboratory from 1978-1985. He did his postdoctoral studies on development of the nervous system at UCSD with Drs. Lily and Yuh Nung Jan (1985-90) and then assumed a faculty position at UCSD in 1990. He is an Alfred P. Sloan and Basil O’Connor Scholar. MARCH 2016 allenfrontiersgroup.org page 1 of 3 FACT SHEET James J. Collins, Ph.D., Massachusetts Institute of Technology, “Synthetic Biology Approaches to Antimicrobial Resistance” Award amount: $1.5 million Project description: The rise of antibiotic resistance has become a public health crisis. Collins will use principles of synthetic biology to engineer safe, frequently consumed bacteria to detect and kill dangerous bacteria such as those that cause MRSA infections, the most frequently identified drug- resistant pathogen in United States hospitals. His novel strategy of rapidly re- designing beneficial changes in bacterial genomes could usher in a new era of design-based medicine. This frontier research will also enable scientists to understand the root causes of antibiotic resistance and the mechanisms by which traditional antibiotics work to target disease. Investigator bio: James J. 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. Professor Collins' patented technologies have been licensed by over 25 biotech, pharma and medical devices 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, as well as several teaching awards. Professor Collins is an elected member of all three national academies—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. Jennifer Doudna, Ph.D., University of California, Berkeley, “Antiviral Machinery and Cell Editing Platforms” Award amount: $1.5 million Project description: Nature has likely evolved multiple methods of host defense, and many remain unknown. Building on her pioneering work to develop Crispr-Cas9 gene editing technology, Doudna will look beyond the typically employed bacterial proteins to similar proteins in diverse organism and also seek out new RNA-targeting strategies. Early research shows that archaea, which can be found in extreme environments with high temperatures, have proteins similar to Cas9 but that may be capable of reaching areas of the genome currently inaccessible in Crispr methods. Targeting RNA would offer a way to edit cell behaviors without targeting the genome directly, opening up a vast new frontier. This work has the potential to introduce novel gene editing technologies to fight human disease, improve agriculture, and promote environmental health. Investigator bio: Jennifer Doudna is the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and she is Professor of Molecular and Cell Biology and Professor of Chemistry at UC Berkeley and an Investigator of the Howard Hughes Medical Institute. Prof. Doudna’s research seeks to understand how RNA molecules control the expression of genetic information. Her research led to insights about CRISPR-Cas9- mediated bacterial immunity that enabled her lab and that of collaborator Emmanuelle Charpentier to re-design MARCH 2016 allenfrontiersgroup.org page 2 of 3 FACT SHEET this system for efficient genome engineering in animals and plants, creating a transformative technology that is revolutionizing the fields of genetics, molecular biology and medicine. She is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the National Academy of Medicine and the National Academy of Inventors. She is a recipient of awards including the NSF Waterman Award, the FNIH Lurie Prize, the Paul Janssen Award for Biomedical Research, the Breakthrough Prize in Life Sciences, the Princess of Asturias Award (Spain), the Gruber Prize in Genetics, the Massry Prize, the Gairdner Award, the Nakasone Prize and the L’Oreal-UNESCO International Prize for Women in Science. Bassem Hassan, Ph.D., Institut du Cerveau et de la Moelle épinière, Paris, “How Developmental Noise in Neural Circuit Development Determines the Unique Behavior of Individuals” Award amount: $1.5 million Project description: Even though we all share fundamental neurological properties, the details of individual neural circuits can vary dramatically among individuals. Hassan has pinpointed a neural circuit in flies that serves as an ideal testing ground for understanding how molecular noise sculpts individual neural circuits during maturation and development. Unraveling the causal link between the dynamic wiring of neural circuits during development and the emergence of behavioral variability will help determine the origin of individual differences within a population, and how individual variations contribute to the fitness of the entire population. The work ultimately will shed light on what makes each of us distinct. Investigator bio: Bassem Hassan is currently a Team Leader at the ICM in Paris, France. During 2016 the Hassan lab will be transitioning to the ICM from the VIB Institute’s Center for the Biology of Disease and the University of Leuven School of Medicine, in Leuven Belgium, where Bassem is a senior group leader and professor at the faulty of medicine. He obtained his Bachelor of Science degree in Biology at the American University of Beirut, Lebanon, and his Ph.D. in Molecular Genetics at The Ohio State University in 1996. Between 1996 and 2001 he was a Howard Hughes Medical Institute and then an NIH Postdoctoral Fellow at Baylor College of Medicine in Houston, Texas working with Drs. Hugo J. Bellen and Huda Y. Zoghbi on the transcriptional mechanisms of early neurogenesis in Drosophila and mouse. In late 2001 he was recruited to VIB to establish the first Drosophila lab in the country, and in 2016 he was recruited to ICM to establish the laboratory of Brain Development. In 2003 he received the European Molecular Biology Organization (EMBO) Young Investigator award and in 2009 he was elected EMBO member. In 2016 he was named the Einstein Visiting Fellow

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