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BIOE Seminar Series: Mammalian Synthetic Biology: Foundation and Therapeutic Applications

Event Type
Seminar/Symposium
Sponsor
Bioengineering
Virtual
wifi event
Date
Mar 8, 2022   11:30 am - 12:20 pm  
Speaker
Ron Weiss
Views
201
Originating Calendar
Bioengineering calendar

Synthetic biology is revolutionizing how we conceptualize and approach the engineering
of biological systems. Recent advances in the field are allowing us to expand beyond the
construction and analysis of small gene networks towards the implementation of complex
multicellular systems with a variety of applications. In this talk I will describe our integrated
computational / experimental approach to engineering complex behavior in a variety of
cells, with a focus on mammalian cells. In our research, we appropriate design principles
from electrical engineering and other established fields. These principles include
abstraction, standardization, modularity, and computer aided design. But we also spend
considerable effort towards understanding what makes synthetic biology different from all
other existing engineering disciplines and discovering new design and construction rules
that are effective for this unique discipline. We will briefly describe the implementation of
genetic circuits and modules with finely-tuned digital and analog behavior and the use of
artificial cell-cell communication to coordinate the behavior of cell populations. The first
system to be presented is a multi-input genetic circuit that can detect and destroy specific
cancer cells based on the presence or absence of specific biomarkers in the cell. We will
also discuss preliminary experimental results for obtaining precise spatiotemporal control
over stem cell differentiation for tissue engineering applications. We present a novel
approach for generating and then co-differentiating hiPSC-derived progenitors with a
genetically engineered pulse of GATA-binding protein 6 (GATA6) expression. We initiate
rapid emergence of all three germ layers as a combined function of GATA6 expression
levels and tissue context. We ultimately obtain a complex tissue that recapitulates early
developmental processes and exhibits a liver bud-like phenotype that includes
haematopoietic and stromal cells, as well as a neuronal niche. This complex organoid
can be used for drug development and potentially for tissue transplantation.

Ron Weiss is Professor in the Department of Biological Engineering and in the Department of
Electrical Engineering and Computer Science at the Massachusetts Institute of Technology, and
is the Director of the Synthetic Biology Center at MIT. Professor Weiss is one of the pioneers of
synthetic biology. He has been engaged in synthetic biology research since 1996 when he was
a graduate student at MIT and where he helped set up a wet-lab in the Electrical Engineering and
Computer Science Department. After completion of his Ph.D., Weiss joined the faculty at Princeton
University, and then returned to MIT in 2009 to take on a faculty position in the Department of
Biological Engineering and the Department of Electrical Engineering and Computer Science. The
research pursued by Weiss since those early days has placed him in a position of leadership in
the field, as evidenced both by publications from his lab as well as a variety of awards and other
forms of recognition. He pursued several aspects of synthetic biology, including synthesis of gene
networks engineered to perform in vivo analog and digital logic computation. The Weiss lab also
published seminal papers in synthetic biology focused on programming cell aggregates to perform
coordinated tasks using engineered cell-cell communication with chemical diffusion mechanisms
such as quorum sensing. Several of these manuscripts were featured in a Nature special
collection of a select number of synthetic biology papers reflecting on the first 10 years of synthetic
biology. While work in the Weiss lab began mostly with prokaryotes, during the last few years a
majority of the research in the lab shifted to mammalian synthetic biology. The lab focuses both
on foundational research, e.g. creating general methods to improve our ability to engineering
biological systems, as well as pursuing specific health related applications such as cancer
immunotherapy and programmable organoids where synthetic biology provides unique
capabilities.

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