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MEMP - Thesis Defense - Harold McNamara

Tuesday, September 3, 2019

Synthetic Physiology: Manipulating and measuring biological pattern formation with light

It is an outstanding challenge to determine how intracellular signaling pathways utilize mathematical principles (e.g. from control theory or statistical physics) in order to achieve robust pattern formation. By pairing optogenetic perturbation with simultaneous optical measurement of biological dynamics, one can create high-dimensional optical interfaces to study complex physiology in multicellular systems.

The first portion of this thesis presents ‘synthetic electrophysiology’, a framework for studying bioelectrical pattern formation.  By deploying all-optical electrophysiology in engineered tissues with designed electrical components, we study electrical tissues as dynamical systems.  In tissues comprised of synthetic excitable cells, we show that geometry is a fundamental determinant of stability and chaos in biological pacemakers, and that excitable cells can be composed in bioelectric circuits capable of primitive information processing and memory.  We also show that electrically bistable issues can form reaction-diffusion patterns of electrical domains which undergo phase transitions via spontaneous symmetry breaking.  These previously unobserved classes of stable electrical patterns suggest a potential role for electrophysiology during embryonic development.
 
The second portion of this thesis describes the development of new tools for optical manipulation and measurement of morphogen pathways in the embryo.  First, we describe a new optogenetic platform for patterning the Nodal morphogen signal in the zebrafish embryo.  Next, we present a new platform for using photochemical patterning of DNA barcodes to layer spatial information onto droplet microfluidics-based single cell RNA sequencing (scRNAseq) methods.  Combing optogenetic morphogen patterning with spatially resolved transcriptomics may enable more powerful studies of how the embryo processes dynamical signals.

Thesis Committee Chair:
Adam E. Cohen, PhD
Professor of Chemistry and Chemical Biology and of Physics, Harvard University

Thesis Committee:
L. Mahadevan, PhD
Professor of Physics; Lola England de Valpine Professor of Applied Mathematics; Professor of Organismic and Evolutionary Biology, Harvard University

Olivier Pourquie, PhD
Professor of Genetics, Harvard Medical School; Professor of Pathology, Brigham and Women’s Hospital

Nicholas Bellono, PhD
Assistant Professor of Molecular and Cellular Biology, Harvard University

 
 
Date and Time: 
Tuesday, September 3, 2019 - 3:00pm
Location: 

Harvard Northwest Building, Room B101 (changed from Harvard Science Center, Lecture Hall E)