Single-cell approaches are revolutionizing biology. Thanks to live imaging we can trace in time the behavior of each cell in a developing organism (1). In parallel, single-cell transcriptomics and genomics gives access to the transcriptional state of each cell (2). Combination of these two approaches promises to unravel how genomic information translates into individual cell behaviours.
Our group is harnessing these approaches to a particularly attractive class of embryos: those of a class of marine invertebrate chordates, the ascidians (Tunicates, 3,4). These embryos develop with such stereotyped cell lineages that each cell of an embryo of one species has an exact match in an embryo of a different, even distantly related, species. Contrasting with this extraordinary morphological conservation, the genomes of ascidians are widely divergent. The proposed project seeks to understand how slow morphological evolution is compatible with fast molecular evolution. We will focus on two classes of genes, the gene regulatory networks (GRN) driving development and the effector genes controlling cell behaviours through cytoskeletal architecture.
The selected student will first establish single-cell RNA-seq for a range of developmental stages in 4 ascidians and 2 thaliaceans (a different class of tunicates, 5). From this dataset, She/He will analyse the level of conservation of the transcriptional programme across species, which could lead to a classification of genes/subnetworks according to their level of expression conservation. In a second step, she/he will select a few genes based on their pattern of expression conservation and their functional annotation and study their function in cell fate specification or embryonic morphogenesis using CRISPR/Cas9 technology.
The project is mostly experimental. Bioinformatics knowledge or a desire to acquire it will be a plus. More about the host group and institute can be found on the CRBM website:
http://www.crbm.cnrs.fr/
References:
1) L. Guignard*, U.-M. Fiuza*, B. Leggio, E. Faure, J. Laussu, L. Hufnagel, G. Malandain, C. Godin#, P. Lemaire# (2017) Contact-dependent cell communications drive morphological invariance during ascidian embryogenesis. bioRxiv 238741
https://www.biorxiv.org/content/early/2017/12/24/2387412) Karaiskos N, Wahle P, Alles J, Boltengagen A, Ayoub S, Kipar C, Kocks C, Rajewsky N, Zinzen RP (2017) The Drosophila embryo at single-cell transcriptome resolution. Science. 358:194-199
3) Lemaire P. (2011) Evolutionary crossroads in developmental biology: the tunicates, Development, 138(11):2143-52.
4) Lemaire P. (2009) Unfolding a chordate developmental program, one cell at a time: Invariant cell lineages, short-range inductions and evolutionary plasticity in ascidians. Developmental Biology ;332(1):48-60.
5) Piette, J. and Lemaire, P. (2015) Thaliaceans, the neglected pelagic relatives of ascidians: a developmental and evolutionary enigma. The Quarterly Review of Biology. 90(2):117-145.
