Programme Post-Doc Bienvenüe Bretagne

The BIENVENÜE post-doctoral program "Welcoming highly-talented international post-docs in Brittany", supported by the Brittany Region, in partnership with 8 higher education and research institutions in Brittany, provides for the recruitment of 75 post-doctoral students with a high international profile in Brittany laboratories.

Decoding the molecular and cellular mechanisms governing Drosophila muscle stem cells maintenance and activation

Host team
Boukhatmi team. The muscle Development and Repair team 

Abstract
Muscle stem (satellite) cells (MuSCs) ensure the functional homeostasis of skeletal muscles as well as their regeneration upon injury. The project goal is to understand how MuSCs sense signals provided by their environment and engage a series of dramatic changes in cellular organization and fate, to repair the muscles. To interrogate these processes, the candidate will take the advantage of newly designed Drosophila transgenic tools and imaging approaches to track MuSCs in vivo and identify genes regulating their behavior during muscle repair.

Keywords
Muscle, Satellite Cells, Stem Cells, Drosophila, Regeneration

Expected profile
The candidate should have a PhD in Life Sciences and interest in studying muscle development and regeneration. Candidates with strong experience in cell/developmental biology, fly genetics, genome wide analysis and in vivo live imaging are encouraged to apply.

References

  • Hadi Boukhatmi. Drosophila, an Integrative Model to Study the Features of Muscle Stem Cells in Development and Regeneration. Cells. https://www.mdpi.com/2073-4409/10/8/2112
  • Hadi Boukhatmi, Torcato Martins, Zoe Pillidge, Tsveta Kamenova and Sarah Bray (2020). Notch mediates inter-tissue communication to promote tumorigenesis. Current Biology 30, 1-12. https://doi.org/10.1016/j.cub.2020.02.088
  • Hadi Boukhatmi and Sarah Bray (2018). A population of adult satellite-like cells in Drosophila is maintained through a switch in RNA-isoforms. eLife 2018;7:e35954. https://elifesciences.org/articles/35954

Team website
https://www.boukhatmilab.com/

Email address to send the application
hadi.boukhatmi@univ-rennes1.fr


 

 

Smart automated microscopy for high content screening in multiplex FRET by FLIM

Host team
Tramier lab - Microscopy for Cell Biosensing

Abstract
The "Microscopy for Cell Biosensing" team develops techniques and methods for the dynamic monitoring of biochemical activities in living cells. The team has developed a fastFLIM prototype, a FRET biosensor of AurkA kinase activities [1] making it possible to discover new functions of this kinase at the mitochondria [2], FRET approaches by FLIM in multiplex [3,4], and a screening methodology for inhibitors of the AurkA kinase by HCS-FLIM [5].
The aim of the post-doctoral position is to obtain unsupervised and automatized sequences of advanced microscopy methods in the context of high content microscopy. We are developing the Roboscope prototype able to analyze in real time acquired images using deep learning algorithms and to feed back to the microscope control module information to adjust the acquisition sequence. The proposed project is to integrate the development of the Roboscope in the pipeline of HCS-FLIM. This kind of approach will be a first step in the development of quantitative automated microscopy for translational research, and pave the way for its use in diagnosis or personalized medicine.

Keywords
Intelligent microscopy, machine learning, quantitative fluorescence microscopy, FRET by FLIM, High Content Screening

Expected profile
We are looking for a talented PhD with expertise in developing microscopy methods applied to biology and a strong interest in machine learning for image analysis.

References

  • Bertolin G, Sizaire F, Herbomel G, Reboutier D, Prigent C, Tramier M. A FRET biosensor reveals spatiotemporal activation and functions of Aurora kinase A in living cells. Nat Commun. (2016) 7:12674. 

  • Bertolin G, Bulteau AL, Alves-Guerra MC, Burel A, Lavault MT, Gavard O, Le Bras S, Gagné JP, Poirier GG, Le Borgne R, Prigent C, Tramier M. Aurora kinase A localises to mitochondria to control organelle dynamics and energy production. Elife. (2018) 7:e38111.

  • Demeautis C, Sipieter F, Roul J, Chapuis C, Padilla-Parra S, Riquet FB, Tramier M. Multiplexing PKA and ERK1&2 kinases FRET biosensors in living cells using single excitation wavelength dual colour FLIM. Sci Rep. (2017) 7:41026.

  • Ringer P, Weißl A, Cost AL, Freikamp A, Sabass B, Mehlich A, Tramier M, Rief M, Grashoff C. Multiplexing molecular tension sensors reveals piconewton force gradient across talin-1. Nat Methods. (2017) 14:1090-1096.

  • Sizaire F, Le Marchand G, Pécréaux J, Bouchareb O, Tramier M. Automated screening of AURKA activity based on a genetically encoded FRET biosensor using Fluorescence Lifetime Imaging Microscopy. Methods Appl Fluoresc. (2020) 8(2):024006.

Team website
https://igdr.univ-rennes1.fr/en/marc-tramier-group

Email address to send the application
marc.tramier@univ-rennes1.fr


 

Mapping enzyme-substrate relationships in the ubiquitin system

Host team
Rabut team - Ubiquitin system

Abstract
Our group investigates at the molecular level the function and regulation of the ubiquitin system. This system controls the activity and stability of the cellular proteome through the covalent modification of proteins by ubiquitin moieties, a process known as “ubiquitylation”. While proteomic experiments have shown that thousands of proteins can be the targeted by ubiquitylation, the great majority of ubiquitylation events remain uncharacterized. In particular, the enzyme that catalyse ubiquitylation have only been investigated for a very limited subset of ubiquitylated proteins. To address this question, we have devised a protein-fragment complementation assay, which enables us to investigate enzyme-substrate relationships in the ubiquitin system at the proteome level. In this project, we propose to apply this methodology to systematically investigate the substrates of SCF-family ubiquitin ligases. This will enable us to provide a comparative map of biological pathways targeted by these ubiquitin ligases.

Keyword
Ubiquitin, Proteasome, Protein-protein interaction, Systems biology, Proteomics.

Expected profile
Candidates should be highly motivated and demonstrate a strong background in molecular biology and biochemistry. Those with expertise in systems biology, bioinformatics or multidisciplinary approaches are especially encouraged to apply. Previous experience in yeast genetics would be appreciated but is not required.

References

Team website
https://igdr.univ-rennes1.fr/en/rabut

Email address to send the application
gwenael.rabut@univ-rennes1.fr


 

How microtubule rigidity contributes to a robust cell division

Host team
Pécréaux team - Cell Division Reverse Engineering (CeDRE)

Abstract
In contrast to the past view of microtubules (MTs) as passive support for cargo transport or transmitting force, our lab and others revealed the key role of their dynamics during cell division. We showed that they contribute to the mitotic-spindle robust positioning in the C. elegans one-cell embryo through a mechano-sensing pathway 1,2, likely calling for regulating MT rigidity 2,3. A candidate is ZYG-8 from doublecortin family that could rigidify MT 4. Its human homolog DCLK1 is overexpressed in many solid tumours. The mechanisms of MT-rigidity regulation could involve (self-repaired) lattice defects, post-translational modifications that stiffen MT, coupling of protofilaments or bundling of MTs 5. It all suggests that MT lattice and bending rigidity must be controlled to ensure cell division robustness. 1) We aim to decipher the mechanisms and delineate how important they are for spindle positioning in the C. elegans embryo.  2) We will investigate the link with chromosome partitioning.

Keywords
Cell division / Caenorhabditis elegans embryo / Microtubule mechanics / Advanced optical microscopy / Image processing and data analysis.

Expected profile
The candidate will have research experiences in the field of cellular and molecular biology, and in particular in microtubules and/or cell division demonstrated by publications. Some skills in genetics and optical microscopy are expected. An interest in system biology and biophysics is desired.

References

  • Bouvrais, H., Chesneau, L., Pastezeur, S., Fairbrass, D., Delattre, M., and Pécréaux, J. “Microtubule feedback and LET-99-dependent control of pulling forces ensure robust spindle position.” Biophysical Journal, 2018.
  • Bouvrais, H., Chesneau, L., Le Cunff, Y., Fairbrass, D., Soler, N., Pastezeur, S., Pécot, T., Kervrann, C., and Pécréaux, J. “The coordination of spindle-positioning forces during the asymmetric division of the C. elegans zygote is revealed by distinct microtubule dynamics at the cortex.” EMBO Reports, 2021.
  • Pécréaux, J., Redemann, S., Alayan, Z., Mercat, B., Pastezeur, S., Garzon-Coral, C., Hyman, A.A., and Howard, J. “The mitotic spindle in the one-cell C. elegans embryo is positioned with high precision and stability.” Biophysical Journal, 2016.
  • Jean, D.C., Baas, P.W, and Black, M.M. “A novel role for doublecortin and doublecortin-like kinase in regulating growth cone microtubules.”  Human molecular genetics, 2012.
  • Hawkins, T.M., Mirigian, M., Selcuk Yasar, M., and Ross, J.L. “Mechanics of microtubules.” Journal of biomechanics, 2010.

Team website
http://pecreaux.openwetware.org/
https://igdr.univ-rennes1.fr/equipe-cedre

Email address to send the application
helene.bouvrais@univ-rennes1.fr


 

RNA controls in development and disease

Host team
Paillard team - Gene Expression and Development

Abstract
Controls of gene expression exerted at the RNA level (alternative splicing, mRNA translation and decay) are instrumental for the development of vertebrate embryos. Our group uses a diversity of in vivo (Xenopus, mice), in cellulo (2D and 3D cultures) and in vitro models. We focus on defective controls of RNA regulations in two human pathologies:
(i) Cataract (ocular lens clouding, the leading cause of blindness worldwide). We investigate how RNA regulations impact the organisation of the cytoskeleton, to confer the lens fiber cells their specific shape. Ultimately this peculiar organisation is required for lens transparency.
(ii) Head and neck squamous cell carcinomas. We investigate how the synthesis of splice isoforms of transcription factors is controlled, and how these different isoforms affect cell properties.
Applications for postdocs in any of these two thematics are welcome.

Keywords
RNA /splicing / eye / cancer

Expected profile
General interest for molecular genetics. Skills in molecular and cellular biology are mandatory. A capacity to analyse deep sequencing data would be welcome.

References

  • Chesnel F, Couturier A, Alusse A, Gagné JP, Poirier GG, Jean D, Boisvert FM, Hascoet P, Paillard L, Arlot-Bonnemains Y, Le Goff X. The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation. PLoS Genet. 2020 Nov 2;16(11):e1009183. doi: 10.1371/journal.pgen.1009183. eCollection 2020 Nov.
  • Aryal S, Viet J, Weatherbee BAT, Siddam AD, Hernandez FG, Gautier-Courteille C, Paillard L, Lachke SA&. The cataract-linked RNA-binding protein Celf1 post-transcriptionally controls the spatiotemporal expression of the key homeodomain transcription factors Pax6 and Prox1 in lens development. Human Genetics 2020 Dec;139(12):1541-1554. doi: 10.1007/s00439-020-02195-7.
  • Viet J, Reboutier D, Hardy S, Lachke SA, Paillard L, Gautier-Courteille C. Modeling ocular lens disease in Xenopus. Dev Dyn. 2020 May;249(5):610-621.
  • Siddam AD, Gautier-Courteille C, Perez-Campos L, Anand D, Kakrana A, Dang CA, Legagneux V, Méreau A, Viet J, Gross JM, Paillard L, Lachke SA. The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development. PLoS Genet. 2018 Mar 22;14(3):e1007278.
  • Noiret M, Méreau A, Angrand G, Bervas M, Gautier-Courteille C, Legagneux V, Deschamps S, Lerivray H, Viet J, Hardy S, Paillard L, Audic Y. Robust identification of Ptbp1-dependent splicing events by a junction-centric approach in Xenopus laevis. Dev Biol 2017 426(2):449-459.

Team website
https://igdr.univ-rennes1.fr/en/gene-expression-and-development-ged-team-leader-luc-paillard

Email address to send the application
luc.paillard@univ-rennes1.fr


 

Recovery of intestinal microvillus atrophy

Host team
Michaux team - Dynamics of epithelial polarity

Abstract
Genetic, inflammatory or pathogenic disorders, as well as aging, can all induce intestinal microvillus atrophy, causing food malabsorption and diarrhoea associated with severe morbidity. However, intestinal microvillus growth and stability during normal development or in pathological contexts has been mostly investigated in vitro. We propose to take advantage of live super-resolution microscopy and endogenously expressed probes to molecularly describe C. elegans inherited, acquired or acute microvillus atrophy models and then identify and characterize new recovery mechanisms.

Keyword
Polarity, microvilli, intestinal diseases

Expected profile
Candidates should demonstrate a strong background in developmental cell biology and imaging.

References (max 5 articles)

  • Bidaud-Meynard A, Demouchy F, Nicolle O, Pacquelet A, Michaux G. High resolution dynamic mapping of the C. elegans intestinal brush border. 2021, BioRxiv, doi.org/10.1101/2021.06.14.448317.
  • Bidaud-Meynard A, Nicolle O, Heck M, Michaux G. V0-ATPase-dependent apical trafficking maintains the polarity of the intestinal absorptive membrane. 2019, Development, 146, dev174508
  • Pacquelet A, Jousseaume M, Etienne J, Michaux G. Simultaneous regulation of cytokinetic furrow and nucleus positions by cortical tension contributes to proper DNA segregation during late mitosis. 2019, Curr Biol, 29, 3766-3777.e4
  • Gillard, G, Nicolle O, Brugière T, Prigent S, Pinot M, Michaux G. Force transmission between three tissues controls bipolar planar polarity establishment and morphogenesis. 2019, Curr Biol, 29, 1360-1368
  • Mosa MH, Nicolle O, Maschalidi S, Sepulveda FE, Bidaud-Meynard A, Menche C, Michels BE, Michaux G*, de Saint Basile G* and Farin HF*. Dynamic formation of microvillus inclusions during enterocyte differentiation in Munc18-2 deficient intestinal organoids. 2018, Cell Mol Gastroenterol Hepatol, 6, 477-493.

Team website
https://igdr.univ-rennes1.fr/en/gregoire-michaux-group

Email address to send the application
gmichaux@univ-rennes1.fr


 

Role of Tricellular Junctions in the Acquisition of Epithelial Cell Shape and Cell Identity

Host team
Le Borgne team - Epithelia Dynamics and mechanics

Abstract
Epithelia are mosaic tissues acting as mechanical and permeability barriers thanks to intercellular junctions. Junctions are robust to maintain tissue integrity, while remaining plastic, readily remodeled to allow cell intercalation, division, or migration. At three cells corners, tricellular junctions (TCJs), composed of a specific subset of transmembrane proteins, connect neighboring cells. Using Drosophila, we described the assembly of TCJs and the close interactions between BCJs and TCJs required to maintain the integrity of the permeability barrier. In addition, we found that loss of TCJ components affects the distribution of adherens junction components, the dynamics of actomyosin and impact mechanical properties, shape and proliferation of cells. This project aims to investigate how TCJs generate and integrate mechanical signals. The working hypothesis is that through signaling, TCJs control actomyosin network to regulate tissue integrity, growth and cell-cell communication.

Keywords
Epithelia, cellular junctions, forces, biophysics, Notch signaling

Expected profile
Expertise in genetics and cell biology, quantitative imaging on living animals, automatic segmentation and mathematical modeling, photo-manipulation tools combining force measurements (laser nano-ablation, optical trap) and photo-conversion of probes expressed at endogenous levels.

References

  • Bazooka/Par3 cooperates with Sanpodo for the assembly of Notch signaling clusters following asymmetric division of Drosophila sensory organ precursor cells  Elise Houssin, Mathieu Pinot, Karen  Bellec, and Roland Le Borgne (2021)doi: https://doi.org/10.1101/2021.01.19.427226, BioRXiv, under review at eLife
  • Interplay between Anakonda, Gliotactin, and M6 for Tricellular Junction Assembly and Anchoring of Septate Junctions in Drosophila Epithelium. Thomas Esmangart de Bournonville  1 Roland Le Borgne  2  Current Biology  2020 Nov 2;30(21):4245-4253.e4. DOI: 10.1016/j.cub.2020.07.090
  • Coordination of Septate Junctions Assembly and Completion of Cytokinesis in Proliferative Epithelial Tissues Daniel, E., Daudé, M., Kolotuev I., Charish, K., Auld V., Le Borgne R.  Curr Biol. 2018 May 7;28(9):1380-1391.e4. doi: 10.1016/j.cub.2018.03.034. Epub 2018 Apr 26. DOI: 10.1016/j.cub.2018.03.034
  • Drosophila E-cadherin is required for the maintenance of ring canals anchoring to mechanically withstand tissue growth. Loyer N., Kolotuev I., Pinot M., Le Borgne R. Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):12717-22.
  • Septins regulate the contractility of the actomyosin ring to enable adherens junction remodeling during cytokinesis of epithelial cells.  Founounou N, Loyer N and Le Borgne R. Dev Cell. 2013 Feb.

Team website
https://igdr.univ-rennes1.fr/en/roland-le-borgne-group

Email address to send the application
Roland.leborgne@univ-rennes1.fr


 

Analysis of asymmetric stem cell division and tissue proliferation

Host team
Giet team - Cytoskeleton and Cell Proliferation team

Abstract
Most, if not all, adult tissues contain a defined number of undifferentiated asymmetric polarised stem cells. Accurate control of stem cell number and division is crucial to maintain tissue homeostasis and avoid tumour formation. During the past decade, the use of Drosophila melanogaster neural stem cells has been proven to be a great model in cancer stem cell biology. These stem cells polarise during mitosis and establishment of an asymmetric mitotic spindle will lead to the asymmetric repartition of cell fate determinants to generate a small differentiating daughter cell while the larger cell retains the proliferation fate. Our group aims to understand how asymmetric cell division is regulated in this model system. Specifically, we want to address 3 fundamental questions: How an asymmetric mitotic spindle assembly is established to trigger the formation of 2 daughter cells of different size and fate? How mitosis is coordinated with polarity establishment? How these mechanisms impact tissue development?

Keywords
Asymmetric cell division, mitotic spindle, cytoskeleton

Expected profile
We are looking for a motivated post-doc, interested by the spatio-temporal regulation of the drosophila asymmetric cell division. A wide range of cutting edge techniques will be used to decipher these mechanisms, ranging to genetics, live imaging, genome editing, proteomics, and biochemistry. The applicant can contact RG to discuss about the project.

References

  • Renaud Caous, Aude Pascal, Pierre Romé, Laurent Richard-Parpaillon, Roger Karess, and Régis Giet (2015).  Spindle assembly checkpoint inactivation fails to suppress neuroblast tumour formation in aurA mutant Drosophila. Nature Communications 6, Article number: 8879 doi:10.1038/ncomms9879
  • Mathieu Métivier1, Brigette Y. Monroy 3, Emmanuel Gallaud1, Renaud Caous1, Aude Pascal1, Laurent Richard-Parpaillon1, Antoine Guichet2, Kassandra M. Ori-McKenney3 and Régis Giet1*Dual control of Kinesin-1 recruitment to microtubules by Ensconsin/MAP7. BioXriv-325035. (2019). Development. doi: 10.1242/dev.171579
  • Mathieu Métivier1, Emmanuel Gallaud1, Aude Pascal1, Jean-Philippe Gagné2, Guy G. Poirier2, Denis Chrétien1, Romain Gibeaux1, Laurent Richard-Parpaillon1, Christelle Benaud1, and Régis Giet1*.  Drosophila dTBCE recruits tubulin around chromatin to promote mitotic spindle assembly. Current Biology. 2020. doi: 10.1016/j.cub.2020.11.009.
  • Peripheral microtubules ensure asymmetric furrow positioning in neural stem cells. Alexandre Thomas, Emmanuel Gallaud, Aude Pascal, Laurence Serre, Isabelle Arnal, 
 Laurent Richard-Parpaillon, Matthew Scott Savoian and Régis Giet. BioXriv. doi: https://doi.org/10.1101/2020.09.10.291112. In revision in « Cell Reports.
  • Emmanuel Gallaud, Laurent Richard-Parpaillon, Aude Pascal, Mathieu Métivier,  Vincent Archambault and  Régis Giet. The spindle assembly checkpoint and the spatial activation of Polo kinase determine the duration of cell division and prevent neural stem cells tumor formation. BioXriv. doi: https://doi.org/10.1101/2021.01.04.425196. Submitted.

Team website
https://igdr.univ-rennes1.fr/en/cytoskeleton-and-cell-proliferation-team

Email address to send the application
Regis.giet@univ-rennes1.fr


 

Structural studies of new toxins targeting the ribosome of the pathogen Mycobacterium tuberculosis

Host team
Gillet team - Ribosomes, Bacteria and Stress

Abstract
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, the leading cause of death due to a single infectious agent, causing more than 1.5 million deaths per year. To survive in the host, protein synthesis (translation) is tightly regulated in Mtb. This is performed by various quality control factors, including ribosome dependent toxins. Although their cellular functions are still largely unknown, many of these systems are strongly induced in response to stress, e.g. drug exposure, hypoxia, eat shock or DNA damage. During this project, we will focus our studies on the structural aspects of new atypical quality control and TA systems impacting the ribosome. Our main objectives are to get structural insights into the binding of these factors to isolated ribosomes and to solve the structure of the complexes in solution by cryo-electron microscopy (cryo-EM).

Keywords
M. tuberculosis; ribosome; toxin; antitoxin; cryo-EM

Expected profile
The candidate is a structural biologist, ideally with cryo-electron microscopy expertise and a background in RNA biology.

References

  • Guyomar C, D’Urso G, Chat S, Guidice E & Gillet R. Structures of tmRNA and SmpB as they transit through the ribosome. Nature Communications 12,4909 (2021) - doi: 10.1038/s41467-021-24881-4
  • Macé, K., Giudice, E., Chat, S. & Gillet, R. The structure of an elongation factor G‐ribosome complex captured in the absence of inhibitors. Nucleic Acids Res. 46, 3211–3217 (2018).
  • Guillet, V. et al. Structural insights into chaperone addiction of toxin‐antitoxin systems. Nat. Commun. 10,782 (2019).

Team website
https://igdr.univ-rennes1.fr/en/reynald-gillet-group-ribosome-bacteria-and-stress

Email address to send the application
Reynald.gillet@univ-rennes1.fr


 

Investigating the mechanisms regulating PARP trapping at sites of DNA damage

Host team
Salbert team - Spatio-temporal regulation of transcription and repair in eukaryotes

Abstract
The poly(ADP-ribose) polymerase PARP1 is a key actor of the DNA damage response [1,2]. It is targeted by inhibitors currently used in the clinic to treat BRCA-deficient tumors. PARP inhibitor (PARPi) cytotoxicity arises from the trapping of the inhibited PARP1 onto the DNA lesions, which prevents further repair step [3]. In this project we aim at gaining insights on the mechanisms that modulate the efficiency of clinically-relevant PARPi by regulating the dissipation kinetics of PARP1 from the DNA lesions. To reach this objective, the first step of the project is to set-up a quantitative framework based on fluorescence microscopy to characterize more precisely PARP1 turnover at sites of damage [4]. Using this framework, the post-doctoral fellow will investigate new mechanisms that could modulate PARP1 trapping with a focus on i) chromatin remodeling processes occurring in the vicinity of the lesions and ii) cofactors of PARP1 that regulate its catalytic activity.

Keywords
DNA repair,  poly(ADP-ribose) polymerase, fluorescence microscopy, chromatin

Expected profile
The candidate should hold a PhD in cell biology or cell biophysics. A extended experience in fluorescence microscopy methods is a prerequisite. Good knowledge in the DNA repair field will also be an asset.

References

  • Sellou H., T. Lebeaupin, C. Chapuis, R. Smith, A. Hegele, H. R. Singh, M. Kozlowski, S. Bultmann, A. G. Ladurner, G. Timinszky*, and S. Huet*. 2016. The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage. Molecular Biology of the Cell. 27(24):3791-3799.
  • Smith R., H. Sellou, C. Chapuis, S. Huet* and G. Timinszky* 2018. CHD3 and CHD4 recruitment and chromatin remodeling activity at DNA breaks is promoted by early poly(ADP-ribose)-dependent chromatin relaxation. Nucleic Acids Research. 46 (12), 6087-6098
  • Juhász S., R. Smith, T. Schauer, D. Spekhardt, H. Mamar, S. Zentout, C. Chapuis, S. Huet* and G. Timinszky*. 2020. The chromatin remodeler ALC1 underlies resistance to PARP inhibitor treatment. Science Advances. 6(51):eabb8626.
  • Smith R., T. Lebeaupin, S. Juhász, C. Chapuis, O. D’Augustin, S. Dutertre, P. Burkovics, C. Biertümpfel, G. Timinszky*, S. Huet*. 2019. Poly (ADP-ribose)-dependent chromatin unfolding facilitates the association of DNA-binding proteins with DNA at sites of damage. Nucleic Acids Research. 47(21):11250-11267

*co-corresponding authors

Team website
https://igdr.univ-rennes1.fr/en/gilles-salbert-group-sprte

Email address to send the application
sebastien.huet@univ-rennes1.fr


 

 

 

Solving forebrain disorders and diagnostic impasse with human iPSCs-derived organoids

Host team
Dupé team - Genetics of disorders related to neurectodermal development

Abstract
The research team investigates biological processes that governs brain establishment during early steps of development and focuses on neurodevelopmental disorders to establish their causes at molecular and cellular levels. The project goal is to use the brain organoid technology to study physiopathology of congenital brain disorders related to Sonic Hedgehog-deficiency. It aims to propose a new molecular diagnostic tool to the patient suffering from this pathology by creating a reference transcriptomic ID card of iPSC derived forebrain organoids recapitulating the forebrain spectrum disorder.

Keywords
Forebrain development, iPSC, SHH, rare genetics disease, RNAseq

Expected profile
The project will involve a range of methodologies in molecular and cell biology. The applicants will have strong molecular/cell biology skills. An interest in developmental biology would be appreciated.

References

  • Kim et al., Brain, 2020, doi: 10.1093/brain/awaa152.
  • Hamdi-Rozé et al., JCEM, 2020, doi: 10.1210/clinem/dgaa249.
  • Kim et al., Brain, 2019, doi: 10.1093/brain/awy290.
  • Dubourg et al., 2018, doi: 10.1002/ajmg.c.31619.

Team website
https://igdr.univ-rennes1.fr/en/genetics-disorders-related-neurectodermal-development

Email address to send the application
valerie.dupe@univ-rennes1.fr


Logo