Abstract: The process of cell fate reprogramming allows to generate patient-specific cells of the type in need, unleashing tremendous possibilities for regenerative medicine, cell therapy, and beyond. Cell fate reprogramming often requires accurate temporal control of the levels of fate-specific proteins, called transcription factors, inside the cell in order to efficiently generate high quality output cells. However, accurate control of cellular concentrations has been out of reach so far, with practitioners injecting these factors at constant rates, without any control over their cellular concentration. In the past decade, advances in engineering biology have made it possible to implement nonlinear controllers that autonomously regulate the level of target molecules inside the cell. In this talk, I will describe critical advances in this direction, focusing mostly on our own work. In particular, I will introduce designs of quasi-integral feedback and feedforward controllers in mammalian cells to achieve set-point regulation of cellular protein levels robustly to disturbances. I will then put some of our controllers in action to uncover optimal trajectories conducive to pluripotent stem cells and as a tool to enforce optimal transcription factor levels during reprogramming. This is the first instance in which sophisticated biomolecular controllers are used for cell fate reprogramming. With this work, we have set the foundations for future research on the engineering of biomolecular networks as controllers of complicated biological processes.
Bio: Domitilla Del Vecchio received the Ph. D. degree in Control and Dynamical Systems from the California Institute of Technology, Pasadena, and the Laurea degree in Electrical Engineering (Automation) from the University of Rome at Tor Vergata in 2005 and 1999, respectively. From 2006 to 2010, she was an Assistant Professor in the Department of Electrical Engineering and Computer Science and in the Center for Computational Medicine and Bioinformatics at the University of Michigan, Ann Arbor. In 2010, she joined the Department of Mechanical Engineering at the Massachusetts Institute of Technology (MIT), where she is currently the Grover M. Hermann Professor in Health Sciences and Technology and a Professor of Mechanical and Biological Engineering. She was awarded a 2024 Vannevar Bush Faculty Fellowship, she is a Fellow of the International Federation of Automatic Control (2022), an IEEE Fellow (2021), a recipient of the Newton Award for Transformative Ideas during the COVID-19 Pandemic (2020), the 2016 Bose Research Award (MIT), the Donald P. Eckman Award from the American Automatic Control Council (2010), the NSF Career Award (2007), the American Control Conference Best Student Paper Award (2004), and the Bank of Italy Fellowship (2000). Her research focuses on developing modeling and biological engineering techniques to understand and control the behavior of genetic circuits in bacterial and mammalian cells. Her lab is particularly interested in applications to biosensing and regenerative medicine.
Host: Joseph Moore
*Reception to follow in Levering Hall