Missions

The mission of this postdoctoral fellowship is to establish the mode of action of a surface protein derived from a genetic screen in zebrafish in the metastatic dissemination of human melanoma. The details of its impact on migration and local invasion of melanoma cells, its expression levels in human melanoma, and its molecular function are not known. Three complementary objectives will be pursued: 1) to measure melanoma cell migration and invasion in vivo after inactivation and overexpression of the candidate; 2) to correlate its expression levels with patient survival and tumor stage in human melanoma; 3) to define the candidate's partners and downstream signaling in different models of melanoma in culture.
Our laboratory is committed to discovering new vulnerabilities in cancer cells through a better understanding of the mechanisms leading to the formation of metastases, which represent the main cause of mortality in cancer patients. We are particularly interested in the influence of signals from the tumor microenvironment on the regulation of cell migration and tumor dissemination, and are looking for ways to interfere with these mechanisms for therapeutic purposes. We use powerful genetic tools in zebrafish as well as its high-resolution imaging capabilities to study adhesion signaling in melanoma in hopes of developing innovative therapies against metastatic cancers.

Activities

The successful candidate will work under the supervision of the Team Leader, Julien Ablain, and will be expected to:
• Participate in the design of research aimed at identifying a new regulator of tumor dissemination;
• Develop and optimize experimental protocols to characterize the role of candidate genes in cell migration and metastasis formation;
• Conduct in vitro and in vivo experiments using genetics, cell and molecular biology, biochemistry and histology techniques including genetic manipulations (RNA interference, CRISPR), transcriptomic and proteomic approaches, protein analyses (immunostaining, Western Blotting, immunoprecipitation, purification), imaging (real-time and/or high-resolution confocal microscopy) and pharmacological studies in different zebrafish models, human cell lines and patient samples;
• Analyze and communicate data in the form of written reports and oral presentations;
• Supervise students and technical staff;
• Write scientific articles describing the results generated for publication.

Skills

• Theoretical and practical knowledge of cancer biology;
• Experience with basic methods in genetics, molecular and cell biology, biochemistry and microscopy;
• Mastery of cell culture techniques;
• Motivation, autonomy, rigor, creativity;
• Communication and teamwork skills;
• Ability to take initiative, manage emergencies and prioritize work;
• Excellent level of English (written and oral);
• Training in animal experimentation.

Results and controls

The outcome of the project will be a model of the molecular and cellular impact of the gene of interest on melanoma cell dissemination.
Progress will be monitored on a task-by-task basis at biweekly meetings with the team leader, based on a predefined Gantt chart. A team presentation and overall project review will take place every 3 months. The deliverables for each task and the deadline for obtaining them are established for each objective:
1) Develop an intravital imaging protocol in primary melanomas genetically modified for the gene of interest in zebrafish;
2) Perform and analyze multi-immunofluorescence experiments on human melanoma sections;
3) Establish the candidate's cellular and molecular mode of action by combining genetic manipulation and real-time imaging, transcriptomic analysis and proteomic analysis in human melanoma and zebrafish cells.

Work Context

The postdoctoral fellow will work in the "Adhesion and Signaling in Metastatic Melanoma" team at the Cancer Research Center of Lyon (CRCL). This is a research team set up at the end of 2020, comprising 2 PhD students, 2 postdoctoral researchers and 2 research assistants, and supported by an appropriate level of funding. CRCL offers a rich scientific environment focused on cancer biology, with 25 research teams and several state-of-the-art core facilities. An aquatics facility is available in Gerland. The proximity of the Leon Berard Comprehensive Cancer Center facilitates interactions with the clinic, and favors collaborations and translational approaches. For more information, http://www.crcl.fr/

Additional Information

Contract will be for 28 months starting September 1 2025. Applications should include a cover letter and a CV with contact information of at least 2 references.