of the PhD thesis project
morphological variation between individuals, between or even within species,
suggests that different tuning of developmental gene regulatory networks (GRNs)
modulates the size and shape of tissues and organs without disrupting their
fundamental organization and function.
the exact mechanisms by which such coordinated – as opposed to pathological -
developmental variation occurs in nature remain largely elusive. We tackle this
question using variation of Drosophila eye size as a model system. In fruit
flies, eye size varies between and within species. We recently demonstrated
that inter and intraspecific variation in eye size can be caused by altering
the proportion of the head primordium directed towards eye fate at the expense
of other head fates, such as antenna or face. Quite unexpectedly, we found out
that this is triggered by varying the time of the onset of eye fate
specification, caused by different temporal regulation of the highly conserved
eye specifying transcription factor, eyeless/PAX6 (Ramaekers et al. Dev. Cell.
aim of this project is to decipher how regulatory networks governing head
development in fruit flies modulate the temporal dynamics of eye fate
specification, ultimately controlling eye size. To this goal, we will first use
single-cell transcriptomics to build an atlas of gene expression during the
specification of the distinct head fates. Based on this set of data, we will
use mathematical modeling to draw hypotheses about the regulation of the temporal
dynamics of eye fate specification which will be tested using genome
engineering techniques such as CRISPR.
project asks fundamental developmental biology questions relevant to both
biomedicine – i.e. what distinguishes “healthy” vs “pathological” morphological
variation and to evolutionary biology – i.e. how is morphological variation
generated. It is highly interdisciplinary and lies at the interface between
systems biology and developmental genetics.
interdisciplinary & intersectoral aspects of the project
This project combines cutting-edge single cell RNA sequencing
techniques, mathematical modeling and genome engineering which must combine a
broad range of expertise, largely represented within the host team and
strengthen by collaborations within the Institut Curie and the nearby ENS.
The selected applicant may also have to spend some time in a
collaborating laboratory in Switzerland, a leading expert in microfluidics
developing methods for single-cell sequencing on small samples. By contributing
to the optimization of pipelines for single cell sequence analyses on small
samples, this project should be beneficial to a broad range of biological
questions, including in the biomedical field. In the longer term, this could
provide support for potential industrial applications.
1. A. Ramaekers*, A. Claeys,
M. Kapun, E. Mouchel-Vielh, D. Potier, S. Weinberger, N. Grillenzoni, D.
Dardalhon-Cuménal, J. Jan, R. Wolf, T. Flatt, E. Buchner, Bassem A. Hassan*,
2019. Altering the temporal regulation of one transcription factor drives
evolutionary trade-offs between head sensory organs. Dev Cell, 50: 780-792.
2. Lucas T, Tran H, Perez Romero CA, Guillou A, Fradin C, Coppey M,
Walczak AM, Dostatni N, 2018. 3
minutes to precisely measure morphogen concentration. PLoS Genet. 2018 Oct
3. Tran H, Desponds J, Perez Romero CA, Coppey M, Fradin C, Dostatni N, Walczak AM. Precision in a
rush: Trade-offs between reproducibility and steepness of the hunchback
expression pattern. PLoS Comput Biol. 2018 Oct 11;14(10): e1006513.
4. S. Weinberger, M. P. Topping, J. Jan, N. De Geest, D. Ozbay, T.
Hassan, X. He, J. T. Albert, B.A. Hassan*, A.
Ramaekers*, 2017. Evolutionary changes in proneural coding sequence quantitatively
regulate sensory organ development and function. Elife 2017 Apr 13;6. pii:
5. C. Oliva, A. Soldano, N. Mora, N. De Geest, A. Claeys, M.-L. Erfurth,
A. Ramaekers, D. Dascenco, D.
Schmucker, N. Sanchez-Soriano, B. A. Hassan, 2016. Regulation of Drosophila
brain wiring by neuropil interactions via a Slit-Robo-RPTP signaling complex.
Dev. Cell. 39 (2): 267-278.