Description:

Ahmad Khalil
Boston University

Title:
The Dark Matter of Synthetic Biology

Abstract:
Synthetic biology aims to predictively reconstruct cellular regulation to control and synthesize biological function. This approach has been successfully applied to explore and engineer a wide range of cellular systems, but has typically depended on the use of well-established, strongly interacting species to program regulatory interactions. However, cells are full of species that interact weakly to collectively produce large and important effects, as well as forms of regulation that have been largely invisible or inaccessible to synthetic biology. I will discuss our efforts to engineer this so-called dark matter of synthetic biology. I will show how weakly interacting molecular species, chemical modifications to chromatin, and disordered proteins can enable us to encode new functions and traits into synthetic biological systems, including epigenetic functions that allow genetically identical cells to exhibit distinct and stably maintained phenotypes.

Bio:
Ahmad (Mo) Khalil is Assistant Professor of Biomedical Engineering and the Associate Director of the Biological Design Center at Boston University, and a Visiting Scholar at the Wyss Institute for Biologically Inspired Engineering at Harvard University. His laboratory develops synthetic biology approaches to examine and engineer the functions of living cells, such as how they make decisions and communicate. He is recipient of numerous awards, including the Presidential Early Career Award for Scientists and Engineers (PECASE), NIH New Innovator Award, NSF CAREER Award, DARPA Young Faculty Award, and a Hartwell Foundation Biomedical Research Award, and has received numerous awards for teaching excellence at both the Department and College levels. Mo was an HHMI Postdoctoral Fellow with Dr. James Collins at Boston University. He obtained his Ph.D. with Dr. Angela Belcher at MIT, and his B.S. (Phi Beta Kappa) from Stanford University.

Description:

Amy Herr
University of California, Berkeley

Title:
Profiling cellular-to-molecular diversity using electrophoretic cytometry

Abstract:
From fundamental biosciences to applied biomedicine, high dimensionality data is increasingly important. In singe-cell measurement tools, microfluidic design has underpinned the throughput, multiplexing and quantitation needed for this rich data. Genomics and transcriptomics are leading examples. Yet, measurement of proteins lags. While proteins and their dynamic forms are the downstream effectors of function, the immunoassay remains the de facto standard (flow cytometry, mass cytometry, immunofluorescence). We posit that to realize the full potential of high-dimensionality cytometry, new approaches to protein measurement are needed.

In this talk, I will describe our ‘electrophoretic cytometry’ tools that increase target selectivity beyond simple immunoassays. Enhanced selectivity is essential for targets that lack high quality immunoreagents – as is the case for the vast majority of protein forms (proteoforms). I will share our results on highly multiplexed single-cell western blotting and single-cell isoelectric focusing that resolves single charge-unit proteoform differences. In fundamental engineering and design, I will discuss how the physics and chemistry accessible in microsystems allows both the “scale-down” of electrophoresis to single cells and the “scale-up” to concurrent analyses of large numbers of cells. Particular emphasis will be placed on precision control of fluids and materials transport in passive systems, with no pumps or valves. Precise reagent control allows for integration of cytometry with sophisticated sample preparation – the unsung hero of measurement science. I will discuss compartment-specific, single-cell western blotting for nucleo-cytoplasmic profiling, which eliminates the need for complex image segmentation algorithms. Lastly, I will link our bioengineering research to driving cytology needs, including understanding the role of protein signaling and truncated isoforms in development of breast cancer drug resistance and understanding protein signaling in individual circulating tumor cells.

Looking forward, I will outline how the microfluidic design strategies developed for cytometry have led us to design and deploy large-format screening platforms for recombinant antibody production. Taken together, we view microfluidic design strategies as key to advancing protein measurement performance needed to address unmet gaps in quantitative biology and precision medicine.

Amy E. Herr is the Lester John & Lynne Dewar Lloyd Distinguished Professor of Bioengineering at the University of California, Berkeley and a Chan Zuckerberg Biohub Investigator. Prior to joining UC Berkeley, she was a staff member at Sandia National Laboratories (Livermore, CA), earned Ph.D. and M.S. degrees in Mechanical Engineering from Stanford University, and completed her B.S. in Engineering and Applied Science with honors from the California Institute of Technology. Her research has been recognized by the NIH New Innovator Award, NSF CAREER Award, Alfred P. Sloan Fellowship (Chemistry), and DARPA Young Faculty Award.

Professor Herr has chaired the Gordon Research Conference (GRC) on the Physics & Chemistry of Microfluidics. She is an elected Fellow of the American Institute of Medical and Biological Engineering (AIMBE), an entrepreneur, and was recently elected to the US National Academy of Inventors. Her research program lies at the intersection of engineering design, analytical chemistry, and targeted proteomics – with a recent focus on cytometry spanning fundamental biological to clinical questions.

Description:

Northwestern's own Dean Julio Ottino

Title: 
Chemical Engineering in the Broader Engineering Ecosystem: A Personal View

Abstract:
“when a field of science is represented by a sphere, intellectual growth occurs not at the center but at the border, where it is in contact with other scientific areas…the sphere representing a particular field of science is in fact a bubble, and those inside the bubble tend to associate almost exclusively among themselves” - JMP 2015

Disciplines grow and invariably they reach crises; every science and engineering discipline goes through these cycles. Having a broader view – looking simultaneously backward and forward – helps put things in perspective. Dean Julio M. Ottino shares his views on these issues, using his own experiences and work as a point of departure, discussing how history can shape ideas and how basic ideas can expand into new domains.

Bio:
Dr. Julio M. Ottino is dean of the Robert R. McCormick School of Engineering and Applied Science at Northwestern University and holds the titles of Distinguished Robert R. McCormick Institute Professor and Walter P. Murphy Professor of Chemical and Biological Engineering. Previously, he was chair of the Department of Chemical and Biological Engineering and founding co-director of NICO, the Northwestern Institute for Complex Systems, run jointly by McCormick and the Kellogg School of Management. Ottino received his PhD in chemical engineering at the University of Minnesota and held positions at UMass/Amherst and chaired and senior appointments at Caltech and Stanford.

Ottino’s research has appeared on the covers of Nature, Science, Scientific American, the Proceedings of the National Academy of Sciences of the USA, and other publications and has impacted fields as diverse as fluid dynamics, granular dynamics, microfluidics, geophysical sciences, and nonlinear dynamics and chaos. A recipient of many awards in the field, Ottino was listed by AIChE as one of the “One Hundred Engineers of the Modern Era" (Post WWII) and was awarded the Fluid Dynamics Prize from the American Physical Society. In 2017, he was awarded the Bernard M. Gordon Prize for Innovation in Engineering and Technology Education from the National Academy of Engineering, regarded as the highest award for engineering education. He is a member of both the National Academy of Engineering and the American Academy of Arts and Sciences.

Description:

Student Presentations
Christine Laramy - Mirkin Group
Matt Kweon - Burghardt Group
Sarah Wood - Mrksich Group

Weekly Seminars given by academic and industry professionals in the fields of Chemical and Biological engineering. 

Student presentations will also occur occasionally during this series.

Description:

Kristala L. J. Prather
Arthur D. Little Professor of Chemical Engineering
Massachusetts Institute of Technology

Enzyme Design and Screening for Metabolic Pathway Engineering

Biological synthesis is increasingly being pursued as an alternative to traditional organic synthesis for the production of chemical compounds. As known biochemical pathways are transferred to non-native hosts and new pathways are designed, access to genes encoding desired enzymatic activities with appropriately high reaction rates is often a limiting factor. In this presentation, I will discuss our efforts to identify enzymes with appropriate activity and selectivity in the context of two novel biosynthetic pathways. In the first example, we have exploited the promiscuous activity of four different enzymes in order to build a versatile platform pathway for the synthesis of various 3-hydroxyalkanoic acids. However, significant activity towards native substrates results in significant levels of undesired byproducts. Working with collaborators, we have generated enzyme variants that display significantly altered specificity towards the desired products. Realizing these results also required the development of new screening methods. Using a second model pathway for the production of glucaric acid, I will describe opportunities to use experimental data to guide the selection of additional enzyme variants that may have higher target activities through a bioprospecting approach that involves network analysis of protein sequences.

Kristala Jones Prather is the Arthur D. Little Professor of Chemical Engineering at MIT. She received an S.B. degree from MIT in 1994 and Ph.D. from the University of California, Berkeley (1999), and worked 4 years in BioProcess Research and Development at the Merck Research Labs prior to joining the faculty of MIT. Her research interests are centered on the design and assembly of recombinant microorganisms for the production of small molecules, with additional efforts in novel bioprocess design approaches. A particular focus is the elucidation of design principles for the production of unnatural organic compounds with engineered control of metabolic flux within the framework of the burgeoning field of synthetic biology. Prather is the recipient of an Office of Naval Research Young Investigator Award (2005), a Technology Review “TR35” Young Innovator Award (2007), a National Science Foundation CAREER Award (2010), the Biochemical Engineering Journal Young Investigator Award (2011), and the Charles Thom Award of the Society for Industrial Microbiology and Biotechnology (2017). Additional honors include selection as the Van Ness Lecturer at Rensselaer Polytechnic Institute (2012), and as a Fellow of the Radcliffe Institute for Advanced Study (2014-2015). Prather has been recognized for excellence in teaching with the C. Michael Mohr Outstanding Faculty Award for Undergraduate Teaching in the Dept. of Chemical Engineering (2006, 2016), the MIT School of Engineering Junior Bose Award for Excellence in Teaching (2010), and through appointment as a MacVicar Faculty Fellow (2014), the highest honor given for undergraduate teaching at MIT.