Interdisciplinary Doctoral Project
Interdisciplinary Doctoral Project

Interdisciplinary Doctoral project in the RAUZI lab (University Côte d’Azur, IBV, Nice) and in the ETIENNE lab (Univ Grenoble Alpes, LIPHY, Grenoble), at the interface between computational physics and biology

Studying the mechanisms and mechanics driving tissue folding

Mophogenesis builds living shapes. A key morphogenetic transformation that shapes tissues and organs is epithelial invagination: a tissue bends and it is eventually internalized transforming the physiological topology of the system. The invagination of epithelial tissues is a vital transformation during embryo development since it is pivotal during embryo gastrulation and neurulation. While much is known of the mechanisms and mechanics driving epithelial flattening (first phase) and bending (second phase), how a tissue is eventually internalized (third phase) is still poorly understood. To tackle this, we propose to use the Drosophila embryo that provides the most advanced genetic tools and study the process of mesoderm internalization. On the computational physics side, we will develop a formal physical framework that can theoretically reproduce morphogenetic processes and predict features of the system that are then back tested experimentally. More specifically, we will design a mechanical model based on active viscoelastic shells and use numerical simulations based on existing tools (e.g., Surface Evolver in 3D) to calculate shell deformations. On the biology side, we will implement multi-view light sheet microscopy coupled to optogenetics and plasma-based laser ablation and image data analysis to characterize and synthetically modulate tissue shape changes to test numerical predictions. The student will be trained on these multiple approaches and techniques to develop an interdisciplinary project focused on uncovering the fundamental principles governing epithelial folding. This knowledge could be used in the future to synthetically build and shape functional organs.The project will be developed in both the Rauzi lab (http://ibv.unice.fr/research-team/rauzi/) and the Etienne lab (http://www-liphy.univ-grenoble-alpes.fr/pagesperso/etienne).

We are seeking a highly motivated and talented candidate to develop this interdisciplinary PhD project. Send a CV, a motivation letter, master scores/ranking and reference letters to matteo.rauzi@univ-cotedazur.fr and jocelyn.etienne@univ-grenoble-alpes.fr

Technician Position in Spinal Cord Regeneration Research
Technician Position in Spinal Cord Regeneration Research

The Cigliola laboratory invites applications for a Research Technician position at the Institute of Biology Valrose in Nice, France. Our lab uses zebrafish and mouse models to study Innate Mechanisms of Spinal Cord Regeneration. We are looking for highly motivated and ambitious candidates with interest for regenerative biology and neuroscience. Enthusiasm for working with animals is essential. Specialized training will be provided. The candidate will have the opportunity to figure as co-author on published manuscripts.

The Institute of Biology Valrose is a research Center of Excellence at the University of Côte d’Azur and offers a vibrant research environment with national and international scientists and collaborations (iBV). Nice is located on the French Riviera and offers amazing opportunities for outdoor recreation.

Technical duties include:

  • Zebrafish breeding, husbandry, and surgeries; molecular biology; generation of mutant or transgenic animals by microinjection.
  • Contribution to research studies, experiments, data collection and assays.
  • Maintenance of general lab supplies; ordering and preparation of reagents and solutions; assistancewith maintaining equipment and lab reagent inventories.
  • Review of laboratory methods manuals.
  • Implementation and supervision of laboratory safety procedures.Required qualifications:Bachelor’s degree in biology or a related field and at least 2-years previous experience in a research lab. The qualified candidate should have strong troubleshooting skills, should be motivated to learn new techniques, organized, and able to work effectively in a team environment. Previous experience with zebrafish is preferred (but not required). Candidates should be fluent in English, as it is the working language in the laboratory.

Please send your application in a single PDF, including (1) a cover letter that includes a description of research interests and experience, (2) CV and (3) contact information of 2 or more references to Valentina CIGLIOLA. Review of applications will begin immediately, and the position will remain open until filled.

PhD Student and Postdoc Positions in Spinal Cord Regeneration Research
PhD Student and Postdoc Positions in Spinal Cord Regeneration Research

The Cigliola laboratory invites applications for PhD Student and Postdoc positions at the Institute of Biology Valrose in Nice, France. Our lab uses zebrafish and mouse models to study Mechanisms of Spinal Cord Regeneration.

While in adult mammals (including humans) spinal cord injury causes lifelong paralysis, zebrafish possess an astounding capacity to regenerate and recover function after a paralyzing injury. We are interested in the following questions: What are the factors and mechanisms allowing innate spinal cord regeneration to occur? How are these mechanisms regulated? Can regeneration in adult mammals be enhanced by re-establishment of innate pro-regenerative programs?

We are looking for curiosity-driven, motivated and ambitious candidates with interest for regenerative biology and neuroscience. We strongly value team spirit, a positive work environment and collaborations. Enthusiasm for working with zebrafish and/or mice is essential. Candidates should be fluent in English, as it is the working language in the laboratory.

The Institute of Biology Valrose is a research Center of Excellence at the University of Côte d’Azur and offers a vibrant research environment with national and international scientists and collaborations (iBV). Nice is located on the French Riviera and offers amazing opportunities for outdoor recreation.

Please send your application in a single PDF, including (1) a cover letter that includes a description of research interests and experience, (2) CV and (3) contact information of 2 or more references to Valentina CIGLIOLA. Review of applications will begin immediately, and the position will remain open until filled.

1 Post-Doctoral position for 2 years - starting Fall 2021
1 Post-Doctoral position for 2 years - starting Fall 2021

Post-doctoral position in Fungal Cell Biology

A 2-year funded postdoctoral position is available fall 2021 at the Institute of Biology Valrose (http://ibv.unice.fr/) of the University of Côte d’Azur, Nice France to investigate the dynamics of polarity establishment in the human fungal pathogen, Candida albicans. C. albicans is a harmless commensal that in response to alterations of its environment can cause superficial as well as life-threatening systemic infections (3). The ability of this organism to switch from an ovoid to a filamentous form is critical for its pathogenicity. This dramatic cell shape change is a distinct advantage for studying cell polarity (1-5). We have recently optimized and established an optogenetic approach in C. albicans filamentous cells that gives us exquisite control of cell polarity in this fungal pathogen (5). In this ANR funded project our goal is to elucidate the interaction between two potential growth sites within the cell, as well as how different membrane compartments contribute to the initiation and stabilization of a new growth. The project will take advantage of cutting-edge imaging approaches, optogenetics and molecular genetics to investigate temporal and spatial control of fungal cell polarity.

We are seeking highly motivated candidates with a background in Cell Biology and previous experience in live-cell imaging. Previous experience in Microbiology is a plus.

Interested candidates can contact R. Arkowitz (arkowitz@unice.fr)

1) C Puerner, A Serrano, RS Wakade, M Bassilana & RA Arkowitz. mBio. 2021 12: e02528-21.
2) C Puerner, N Kukhaleishvili, D Thomson, S Schaub, X Noblin, A Seminara, M Bassilana & RA Arkowitz. BMC Biology.
2020. 18: 122.
3) M Bassilana, C Puerner & RA Arkowitz. Curr. Opin. Cell Biol. 2019 62:150-158.
4) A Weiner, F Orange, S Lacas-Gervais, K Rechav, V Ghugtyal, M Bassilana & RA Arkowitz. Cell Microbiol. 2019 21: e12963
5) PM Silva, C Puerner, A Seminara, M Bassilana & RA Arkowitz. Cell Rep. 2019 28:2231–2245.

PhD position in Fungal Cell Biology
PhD position in Fungal Cell Biology

A funded PhD position is available at the Institute of Biology Valrose, University of Côte d’Azur, Nice France to investigate the molecular mechanisms of antifungal tolerance – pathways linking cytoplasmic crowding to drug accumulation and stress responses in a human fungal pathogen. Initial studies indicate the majority of fatal fungal infections are caused by drug-tolerant strains. Candida albicans is a harmless commensal that in response to alterations of its environment can cause superficial, as well as life-threatening systemic infections. In this ERC funded collaborative project, our goal is to determine the link between antifungal drug tolerance and cytoplasmic crowding at the single cell level. The project will take advantage of cutting-edge imaging approaches, molecular genetics and image analyses to investigate relationship between physical characteristics of the cytoplasm and antifungal tolerance in C. albicans cells and communities.

We are seeking highly motivated candidates with a background in Cell Biology and previous experience in live cell imaging and/or image analyses. Previous experience in Microbiology is a plus.

Interested candidates contact R. Arkowitz (arkowitz@unice.fr)

  • C Puerner, N Kukhaleishvili, D Thomson, S Schaub, X Noblin, S Seminara, M Bassilana & RA Arkowitz. BMC Biol. 18: 122.
  • M Bassilana, C Puerner & RA Curr Opin Cell Biol. 2020 62:150-158.
  • A Weiner, F Orange, S Lacas-Gervais, K Rechav, V Ghugtyal, M Bassilana & RA Cell Microbiol. 2019 21: e12963.
  • PM Silva, C Puerner, A Seminara, M Bassilana & RA Cell Rep. 2019 28:2231–2245.
  • H Labbaoui, S Bogliolo, V Ghugtyal, NV Solis, SG Filler, RA Arkowitz & M Plos Pathog. 2017 13: e1006205.
1 PhD Position in Neurosciences - Deadline Mid-June 2021
1 PhD Position in Neurosciences - Deadline Mid-June 2021

A joint PhD position in Neuroscience is available at the University of Turin (UNITO) and the University Côte d’Azur (UCA) within the framework of the Vinci Program 2020 (Università Italo-Francese/Université Franco-Italienne).

We are seeking for a highly motivated candidate, strongly interested in Experimental Neuroscience and Molecular Neurobiology and dedicated to high quality research. The research project deals with the identification of molecular mechanisms controlling mitochondrial function in postnatal neurogenic niches and their implication in cognitive disorders.

The project will focus on the mitochondrial dysfunction caused by deficiency of the transcriptional regulator Nr2f1 (also known as COUP-TFI) and will address the downstream target genes crucial for mitochondrial function and investigate its outcome on neuronal plasticity and function. Patients with NR2F1 haploinsufficiency     have     mild     to      severe      neurodevelopmental      cognitive      disorders,      such as intellectual deficiency, epilepsy, learning and language impairments. The final goal is to unravel the cellular and molecular mechanisms by which Nr2f1 controls mitochondrial function in neurons and how this is correlated with proper cognitive behavior.

The project will combine multiple methodologies ranging from gold-standard neuroanatomical approaches to advanced techniques, such as tissue clearing, light-sheet microscopy and 3D whole-brain reconstruction, and two-photon functional imaging, as well as genome-wide and in silico analyses and animal behavior.

The successful candidate will enroll as a PhD student in Neuroscience at the University of Turin under the co- direction of Prof. Silvia De Marchis and Dr. Michèle Studer. The candidate needs to have good communication skills in English and willing to work in Italy and France since the project will be carried out in the “Adult Neurogenesis” group at the Neuroscience Institute Cavalieri Ottolenghi at UNITO and in the “Development and Function of Brain Circuits” group at UCA.

The call will open on May 20, 2021 on the UNITO website (deadline for mid-June, 2021 – check the exact deadline on the platform) and the starting date of the PhD program is November 1st, 2021. The position is fully financed for four years.

General information on the organization and activities of the PhD Program can be found on the PhD in Neuroscience website (https://dott-neuroscienze.campusnet.unito.it).

If interested, please contact silvia.demarchis@unito and michele.studer@unice.fr by including an updated and detailed CV and a motivation letter.

 

Relevant publications:

Bonzano S, Crisci I, Podlesny-Drabiniok A, Rolando C, Krezel W, Studer M, De Marchis S. Neuron- Astroglia Cell Fate Decision in the Adult Mouse Hippocampal Neurogenic Niche Is Cell-Intrinsically Controlled by COUP-TFI In Vivo. Cell Rep. 2018 Jul 10;24(2):329-341. doi: 10.1016/j.celrep.2018.06.044.

Flore G, Di Ruberto G, Parisot J, Sannino S, Russo F, Illingworth EA, Studer M, De Leonibus E. Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis. Cereb Cortex. 2017 Feb 1;27(2):1629-1643. doi: 10.1093/cercor/bhv336. PMID: 26813976.

Beckervordersandforth R. Mitochondrial Metabolism-Mediated Regulation of Adult Neurogenesis. Brain Plast. 2017 Nov 9;3(1):73-87. doi: 10.3233/BPL-170044.

1 Post-doctoral position _ Starting January 2021
1 Post-doctoral position _ Starting January 2021

Postdoctoral position in Developmental Neurobiology

Michèle Studer team

A postdoctoral position is available from January 2021 in the “Development and Function of Brain Circuits” team led by M. Studer. We aim to understand how rare genetic variants of key master genes of brain development and circuit assembly can cause neurodevelopmental diseases (NDDs). The project will determine the impact of missense variants identified in the NR2F1 gene on the heterogeneity of neurodevelopmental defects described in affected patients. The postdoc will study genotype/phenotype correlations by using CRISPR/Cas9 gene editing in vivo and decipher the
pathological contribution of representative variants in the mouse system. We expect that the results of this work using experimental systems as well as the identification of Nr2f1 direct targets and interacting partners will help in understanding the phenotypic heterogeneity of patients and unveil pathophysiological mechanisms common to multiple NDDs.

Location

The team is located in the heart of Nice and is part of the Institute of Biology Valrose (27 teams; 300 people; 25 nationalities), an international research centre that brings together high-profile teams with complementary areas of expertise and with a common interest in translating basic research into knowledge for the clinic. The iBV provides state of the art core facilities, with a collaborative and lively atmosphere in a gorgeous city/region. For more information, visit http://ibv.unice.fr/institute/presentation/

Qualification and experience

We are seeking highly motivated young candidates holding a PhD for less than 2 years. Preference will be given to applicants with a background in mouse genetics, cellular and molecular biology, confocal imaging and genome wide approaches. The position is opened for one year renewable up to 3 years (including medical benefits) starting as early as January 2021. Fluency in English is mandatory but ability to speak French is not required.

Applications

Applications should contain a CV, a letter of motivation with a description of research accomplishments (2 pages max) and the contact information of two references able to recommend their research work directly to Michele.STUDER@unice.fr.

Selected related publications :

1. Bertacchi M. et al., EMBO J. 2020 Jun 2. PMID: 32484994
2. Bertacchi M. et al., EMBO Mol Med. 2019 Jul 18. PMID: 31318166
3. Bertacchi M. et al., Review, Brain Res. 2018, Apr 27. PMID: 29709504.
4. Bosch D.G.et al., Am J Hum Genet 2014, Feb 6.. PMID: 24462372

1 Doctoral position in the Vessel Formation in Development and Disease group
1 Doctoral position in the Vessel Formation in Development and Disease group

An ANR funded PhD position is available in the Vessel Formation in Development and Disease group at the iBV

The role of p16-dependent cellular senescence in healthy aging

 

Description :

Cellular senescence attracts attention as a key player contributing to organismal aging. The accumulation of senescent cells is dramatically increased with aging, however their precise contribution to aging-related phenotypes remains largely unclear. In collaboration with the team of D. Bulavin we showed p16-dependent senescent cells are required for healthy aging. We used different novel inducible mouse lines to characterise the role of p16 expressing cells in different organs. Currently, we focussed mainly on liver. The project aims at identifying the cell repertoire linked to aging-induced senescence and to investigate the impact of senescent cells on liver functions and to understand molecular pathways modulated by senescence. For these purposes we will use p16-Cre and p16-Cre-ERT2 mice crossed either with Rosa26-mTmG reporter or Rosa26-DTA ablator mice. The animals will be investigated by histological and immunohistological methods and RNA sequencing will be performed at different ages. This project will help to understand the molecular mechanism responsible for aging-induced activation of senescence and hopefully identify potential molecular targets to manipulate senescence through reprogramming and/or selective elimination of subsets of senescent cells.

Required Skills :        

The working language is English.
Experience in molecular biology, cellular biology and/or mouse genetics would be a plus.
Motivation to work with mouse models and team orientation are required. Animal experimentation training is part of the project.

Related publications:

Grosse, L, Wagner, N, Emelyanov, A, Molina, C, Lacas-Gervais, S, Wagner, KD et al.. Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan. Cell Metab. 2020:. doi: 10.1016/j.cmet.2020.05.002. PubMed PMID:32485135 .

Wagner, KD, Du, S, Martin, L, Leccia, N, Michiels, JF, Wagner, N et al.. Vascular PPARβ/δ Promotes Tumor Angiogenesis and Progression. Cells. 2019;8 (12):. doi: 10.3390/cells8121623. PubMed PMID:31842402 PubMed Central PMC6952835.

Wagner, KD, El Maï, M, Ladomery, M, Belali, T, Leccia, N, Michiels, JF et al.. Altered VEGF Splicing Isoform Balance in Tumor Endothelium Involves Activation of Splicing Factors Srpk1 and Srsf1 by the Wilms' Tumor Suppressor Wt1. Cells. 2019;8 (1):. doi: 10.3390/cells8010041. PubMed PMID:30641926 PubMed Central PMC6356959.

Wagner, KD, Ying, Y, Leong, W, Jiang, J, Hu, X, Chen, Y et al.. The differential spatiotemporal expression pattern of shelterin genes throughout lifespan. Aging (Albany NY). 2017;9 (4):1219-1232. doi: 10.18632/aging.101223. PubMed PMID:28437249 PubMed Central PMC5425123.

Wagner, KD, Cherfils-Vicini, J, Hosen, N, Hohenstein, P, Gilson, E, Hastie, ND et al.. The Wilms' tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression. Nat Commun. 2014;5 :5852. doi: 10.1038/ncomms6852. PubMed PMID:25510679 .

El Maï, M, Wagner, KD, Michiels, JF, Ambrosetti, D, Borderie, A, Destree, S et al.. The Telomeric Protein TRF2 Regulates Angiogenesis by Binding and Activating the PDGFRβ Promoter. Cell Rep. 2014;9 (3):1047-60. doi: 10.1016/j.celrep.2014.09.038. PubMed PMID:25437559 .

Contacts:

Kay-Dietrich Wagner – kwagner@unice.fr
Nicole Wagner – nwagner@unice.fr

 

PhD Position - 3 years - Starting October 2020
PhD Position - 3 years - Starting October 2020

Deciphering the regulation of the cell death receptor Fas by cell polarity molecules & adherens junctions in both tumoral and normal human epithelia

Key words: Receptor, Signaling, Cancer, Cell polarity, Cell-Cell jonctions

 

The PhD student will integrate the research group “death receptors signaling in cancer therapy” (iBV, http://ibv.unice.fr/research-team/hueber). at the Institute of Biology Valrose affiliated to the CNRS, Inserm and University Côte d’Azur (UCA).

Project proposal: Our team is investigating the functions of the cell death receptor Fas/CD95/TNFRSF6, a member of the TNFR superfamily. Fas is considered as a tumor suppressor thanks to its ability to eliminate cancer cells by engaging programmed cell death by apoptosis. However, Fas activation by its ligand (FasL) could also promote tumor development and immune disorders (1). Our group is studying the molecular mechanisms that control the Fas versatile signaling outcome in the context of both normal and cancer cells (2, 3). Our recent data show that formation of adherens junction, a cell-cell adhesion complex, and association with the Dlg1 polarity complex prevent the pro-apoptotic signaling of Fas (4, 5). This new Fas-regulatory mechanism is crucial to protect normal epithelial cells from apoptotic signals and to sense and eliminate abnormal cells from epithelial tissues to prevent pathological outcome such as cancer and chronic inflammatory diseases. The PhD student will pursue this project and decipher the regulation of Fas cell death and non- death signaling by the Cadherin-Dlg1 polarity complex notably by studying Fas receptor signaling/trafficking on both primary and tumoral epithelial human cells by using various cell biology approaches.

Bibliography of the team link to the project: 1- Rossin et al (2019) Cancers, 8;11(5):639. 2- NL t al (2018) Sci Rep, 20;8(1):12424. 3- Chakrabandhu K (2016), PLoS Biol, 4;14(3). 4- Gagnoux-Palacios, L.; et al (2018) Journal of Cell

Biology, 217, 3839-3852. 5- Gagnoux-Palacios L., Hueber AO (2019) Medecine/Sciences. 35(11):830-833.

Technical approaches: Human cell culture; cell death assays; receptor trafficking studies (cell surface labeling, endocytosis assay), protein expression quantification/localization (FACS, IP, IF, IB, ELISA, proteomic); microscopy techniques (confocal imaging, time-lapse).

Candidate profil: We are looking for a highly motivated student, independent and creative, with a Master’s Degree in Cellular, Cancer or Molecular Biology. Prior experience with cell culture and classical cellular and biochemical approaches will be appreciated.

HOW TO APPLY: Interested and motivated students should send as soon as possible a CV, a motivation letter, master scores/ranking and reference letters to both L. GAGNOUX (gagnoux@unice.fr) and A-O HUEBER (hueber@unice.fr).