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Dorrity Group

Environmental response at the single-cell level

The Dorrity group investigates how variability propagates from the level of molecules to developing cells and tissues, and ultimately to organismal phenotype.

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Lab website

Previous and current research

Effects of environmental stress are variable, with some individuals more sensitive than others. This variability obscures the influence of the environment during development, limits our understanding of genotype–phenotype relationships, and leaves us unable to predict how different species will respond to a changing environment. 

To better understand how environmentally induced variability propagates across scales, our lab uses single-cell genomics as a phenotyping tool to capture cell- and organism-level processes alongside molecular phenotypes in ectotherms. We adapt this approach in different fish species, capturing multiscale phenotyping data for hundreds to thousands of individuals to build an average “embryo trajectory” and to quantify reproducibility in development. Using computational and statistical approaches to partition variability at different levels (molecular, cellular, and organismal), we define sources of environmental sensitivity and uncover mechanisms of adaptation. We then validate and explore these mechanisms experimentally using classical developmental genetics, gene editing and time-resolved imaging.

The environment can challenge the embryo’s capacity to coordinate responses across cells. Our previous work has shown that raising zebrafish embryos in elevated water temperatures has profound effects on the programme of development: cell types proportions are altered in the embryo, specific cell types show increased variability across individuals, and development accelerates non-uniformly across cell types. This differential acceleration introduces asynchrony that limits reproducibility of development. These findings reveal how a global perturbation like temperature nevertheless induces cell type-specific effects that underlie whole-animal phenotypes.

At the molecular level, temperature sensitivity is linked to mechanisms of proteostasis–the maintenance of folding, synthesis, and degradation of proteins. While biochemical mechanisms of proteostasis control are well-understood, their differential activity across cell types during the course development is not. We focus on two questions: (1) How do cell type-specific differences in proteostasis affect temperature sensitivity in the embryo? (2) Does control of proteostasis influence developmental rate? We combine single-cell genomics and high-throughput biochemistry to define the parameters that drive sensitivity of different cell lineages, with a long-term goal of engineering increased reproducibility of developmental processes.

Future projects and goals

We use experimental and computational approaches to understand links between temperature sensitivity, developmental timing, and the reproducibility of embryogenesis. Our projects include:

  • Profiling embryos raised in a wide range of environments to identify environmentally sensitive cell types and tissues.
  • Defining molecular processes and regulatory mechanisms underlying cell type-specific differences in developmental rate
  • Engineering stress resilience in the molecular processes that control development
  • Mapping adaptive genetic variation in cell type-specific responses to the environment
Figure 1: Integrating the effects of the environment at multiple scales to identify mechanisms of developmental robustness.
Figure 1: Integrating the effects of the environment at multiple scales to identify mechanisms of developmental robustness. Members of the Dorrity group focus on understanding the role of the environment at the level of molecules, cells, and tissues in zebrafish (Danio rerio) and medaka (Oryzias latipes), and ask how environmental sensing mechanisms determined in the lab may manifest in natural populations adapting to changing environments.
Figure 2: Multiscale phenotyping with single-cell genomics to identify environmentally sensitive developmental processes.
Figure 2: Multiscale phenotyping with single-cell genomics to identify environmentally sensitive developmental processes. Using single-cell genomics data from individually barcoded animals (A), we can use molecular features to measure variation in their (B) anatomical composition and developmental rate in response to environmental perturbations.
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