Quantitative Developmental Biology

Pedro Lombardi / Institut Curie

Wolfgang Keil Team leader Tel:

Development is the process by which the fertilised egg, a single cell, transforms into a fully functional multicellular organism. During this transformation, all basic cellular processes – from the cycle of each cell division to the formation of individual organs – need to be precisely coordinated in time and space. Our team is interested in how this is achieved. Our research is driven by the conviction that mathematical and physical concepts are indispensable for a deeper understanding of how the collective action of gene networks and environmental factors drives the emergence of biological shapes and patterns. Ultimately, we would like to reveal evolutionary conserved principles of patterning in metazoan development and expose novel mechanisms underlying developmental precision and robustness.

 C elegans

Long-term high-resolution imaging of C. elegans larvae with microfluidics. A C. elegans animal immobilized at various post-embryonic stages from L1 (upper left) to L4 (lower right), showing dynamic expression of the miRNA mir-47. Scale bar, 100 um.

We use an interdisciplinary strategy at the interface between physics and biology, employing both experimental and theoretical approaches. Our model organism is the small roundworm Caenorhabditis elegans (C. elegans), a simple multicellular organism with ~1000 cells.  On one end, we develop novel techniques to improve our ability to obtain quantitative high-resolution dynamic data on C. elegans development (live imaging with microfluidics, on-chip perturbations of development, software for automated phenotypic analyses of 4D microscopy data etc.). At the same time, we study a variety of paradigmatic developmental patterning problems in the worm for which high-resolution dynamic imaging data can really transform our understanding of the underlying mechanisms. Finally, we develop theoretical approaches to conceptualise these mechanisms and uncover general principles of development.


image 3

(A) Live Nomarksi and fluorescence microscopy of the first two cell divisions during the development of the C. elegans egg-laying organ. YFP visualizes the dynamics of Notch target gene (lst-5) expression (yellow). (B) Fluorescence intensity (lst-5pro::YFP) as a function of time in the precursor cells of the organ.

Our approach relies on a combination of areas of expertise of the group:

(i) Large scale quantitative live-imaging capturing relevant gene expression and protein dynamics as well as developmental phenotypes (i.e. cell-lineages) during C. elegans development

(ii) Cutting-edge microfluidics technologies for high-resolution long-term live-imaging as well as for delivering precise spatiotemporal perturbations of development on-chip;

(iii) State-of-the-art genome editing tools to generate live reporter strains and mutants

(iv) Software tools for automated high-throughput analyses of developmental phenotypes, including, e.g. tracking of cell divisions, gene expression in C. elegans;

(v) Mathematical modeling of gene expression dynamics and cell-fate decisions processes, making quantitative predictions that are testable in experiments.

Key publications

Year of publication 2021

Stec Natalia, Doerfel Katja, Hills-Muckey Kelly, Ettorre Victoria, Ercan Sevinc, Keil Wolfgang, Hammell Christopher (2021 Feb 22)

An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output

Current Biology : 31 : 809-826.e6 : DOI : https://doi.org/10.1016/j.cub.2020.11.060

Year of publication 2019

Attner MA*, Keil W*, Benavidez JM, Greenwald I (2019 Sep 23)

HLH-2/E2A Expression Links Stochastic and Deterministic Elements of a Cell Fate Decision during C. elegans Gonadogenesis

Current Biology : 29 : 1-7 : DOI : https://doi.org/10.1016/j.cub.2019.07.062
Katz M, Corson F*, Keil W*, Singhal A, Bae A, Lu Y, Liang Y & Shaham S (2019 Apr 23)

Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5

Nature Communications : 10 : DOI : 10.1038/s41467-019-09581-4

Year of publication 2018

Kutscher LM, Keil W, Shaham S (2018 Oct 22)

RAB-35 and ARF-6 GTPases Mediate Engulfment and Clearance Following Linker Cell-Type Death

Developmental Cell : 47 : 222-238 : DOI : 10.1016/j.devcel.2018.08.015

Year of publication 2017

Keil W, Kutscher LM, Shaham S, Siggia ED (2017 Jan 23)

Long-term high-resolution imaging of C. elegans larval development with microfluidics

Developmental Cell : 40 : 202-214 : DOI : 10.1016/j.devcel.2016.11.022
All publications