CIFRE GRANT OFFER

Ph.D. studentship offer

Subject:  “An original pipeline to screen drugs targeting splicing factor s.”

Host laboratory and context:

This thesis is funded for three years (09/2017-08/2020) by a CIFRE contract between the SABNP laboratory (INSERM research unit UMR1204) at Evry University (South suburb of Paris) and the company, Synsight, of the Genopole biocluster for biotechnologies nearby.

The Ph.D. laboratory work will be performed at the SABNP laboratory as part of a research program on pre-mRNA splicing and protein expression at the cellular and molecular levels. Based on a multidisciplinary approach, the SABNP laboratory notably explores the dynamics and structure of RNA/protein complexes. Novel technologies are also currently developed to explore cellular and molecular processes involved in gene expression regulation.

Synsight is a company specialized in molecular modeling, bioinformatics and structural biology fields. Synsight offers high quality services to improve and accelerate research for pharmaceutical and cosmetic industries. In addition, Synsight developed an important R&D program to raise new targets and molecules for the control of gene expression.

Scientific project: Defects in constitutive or alternative pre-mRNA splicing have dramatic consequences on protein expression. Indeed genetic diseases are often associated with mutations of RNA sequences recognized by splicing factors or by mutations or abnormal expression of spliceosomal RNA-Binding Proteins (RBPs). However, despite the evidence for the pervasive role of splicing defects in diseases, only few molecules that target the spliceosome have been developed so far. Based on a virtual pharmacophore screening approach several molecules have been selected from larges libraries by Synsightcompany as candidate to interfere with splicing factors interactions.

The Ph.D. student will combine biochemical, structural, cellular and high throughput gene expression approaches to characterize the actions of these molecules on splicing factors interactions and on pre-mRNA splicing.

Developing such molecules opens novel perspectives to study the functions of splicing factors that are affected in diseases and holds promises as therapeutic agents in particular for cancer, neurodevelopment and neurodegenerative diseases.

Keywords : pre-mRNA splicing, splicing inhibitors, splicing correction, RNA Binding Proteins, Protein-protein interactions, protein structure, genetic diseases, cancer.

Candidate profile: Candidates should have a master 2 degree or equivalent in September 2017 and be highly motivated individuals with knowledge in molecular and cellular biology.French skillsare not required if the candidate is fluent in English.

Co-supervisors : David PASTRE and Alexandre MAUCUER

Contact: Letter stating your interest plus CV to be sent to lydia.lebouil@univ-evry.fr