The Biophysics of Organismal Development

Project: Research project

Project Details

Description

In spite of the progress in molecular biology over the last 3 decades,1 we are still searching for the mechanisms
that generate complex spatial patterns of cellular differentiation and morphology. While the core patterning genes -
those responsible for laying out the blueprint of the body plan - are small in number and strikingly conserved, the number
of molecules involved in reading and executing the blueprint is vast. Central to “reading of the blueprint” are thousands of
proteins and regulatory genes participating in the patterning of physical forces that give rise to complex spatial patterns of
gene expression and morphology. The physical and chemical form of multicellular organisms is therefore a complex trait.
Addressing complex traits requires a phenomenological treatment, juxtaposing the kinds of analyses that help us understand
why some people have blue eyes - a decidedly Mendelian and simple trait. From this point of view, the approach I propose
bears a striking resemblance to Condensed Matter Physics, which studies the emergent macroscopic properties of materials
that are a collection of a vast number of molecular components. With this in my mind, my work is focused on constructing
measurement tools and models for organismal development from a necessarily phenomenological perspective. In particular,
models form the bases of inference schemes that permit the quantitative measurement of biophysical parameters directly
from live-imaging data, which we do not have direct experimental access to. Combining these biophysical measurements
with fluorescent proxies for genetic and protein activity permits the construction of mathematical models for organismal
dynamics at the scales they are manifest. New models form the bases of future hypotheses, experimental predictions, and
inference schemes. Central to my work is the development of image analysis tools, and collaborations with experimental
labs around the world with an expertise in live-imaging. Below are the descriptions of two such research directions. Epithelial Patterning, Tissue Mechanics, and Mechanotransduction: The precise developmental patterns of sensory
tissues, such as the eye and the inner ear, are central to faithfully transducing physical signals into biological activity.
Sensory tissues therefore provide an ideal setting within which to study the synchronous emergence of complex patterns of
gene expression and morphology. In collaboration with the Carthew Lab (Northwestern Univ.), we are focused on a twoday
period of larval eye development in the fruit fly - Drosophila. Fig.1A shows the patterns of individual optical units,
ommatidia, that will eventually comprise the compound Drosophila eye. The tissue transitions from a disorganized group of
cells to a patterned, near crystalline, epithelial tissue via a moving mechanical wave called the morphogenetic furrow (MF).
Cells do not migrate into the furrow but rather the furrow moves across the field as a mechanical trigger wave over a two-day
period - right to left in Fig. 1A. Within the MF, cell division ceases and periodic groups of cells undergo a stereotyped
cascade of differentiation. The result of these dynamics is that each ommatidia contains a cluster of 8 distinct (in terms
of the genes expressed) photoreceptor cells surrounded by support and pigment cells. Stereotypy in cellular differentiation
goes hand in hand with stereotypy in cellular and tissue morphology: rows of cells buckle to form hairpin-like structures,
which eventually form circular cages comprising a single optical
StatusActive
Effective start/end date8/1/167/31/21

Funding

  • Simons Foundation (409597)

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