Phd Fellowship In Bioinformatics
Reference : PhD Gilles Travé
Publication de l'offre : 10 octobre 2016
The Department of Integrative Structural Biology, of the Institut de Biologie Moléculaire et Cellulaire (IGBMC-CERBM), University of Strasbourg, is pleased to announce that a three-year PhD fellowship will be available from 1 February 2017 or as soon as possible thereafter. The application deadline is 30 November 2016.
Applications are invited from applicants who hold or expect to hold a master´s degree in bioinformatics, to perform the following PhD project: Hijacking of human PDZ domains by viral proteins.
Many protein-protein interactions are mediated by "domain-motif interactomes", i.e. networks of globular domains binding to short linear amino-acid sequence motifs, in complex intracellular competitions that depend on individual binding affinities. Pathogens such as viruses have developed strategies to "hijack" particular cellular functions by interfering with host domain-motif interactomes involved in these functions. A prototypical example is given by the interference of viral proteins with human PDZ domains. PDZ domains are a family of globular domains that recognize short linear motifs bearing a specific consensus sequence at the extreme C-terminus of their target proteins. The human proteome counts 266 PDZ domains dispersed over 152 proteins, and about 5000 putative PBMs (PDZ-binding motifs). PDZ-PBM interactions often participate in cell adhesion and polarity processes critical for cellular differentiation, proliferation and migration. Remarkably, many viral proteins contain PBMs that target PDZ-containing cellular proteins.
We are an experimental team interested in the human PDZ-PBM interactome and its hijacking by viral proteins. In an effort to address this topic in a quantitative manner, the team is developing methods that not only identify domain-motif interactions, but also evaluate their affinity constants. This allows comparing and ranking all interactions based on interaction strength, rather than just providing a binary information ("bind" or "does not bind"). The team has already published a chromatographic approach, called the "holdup assay" which allows measuring up to 1000 affinities per day (Vincentelli et al., Nature Method 2015). The team has also cloned and expressed a library containing the 266 human domains (the "PDZome") which can be used to measure the binding of any PBM of interest to the entire human PDZome.
In this project, we will further develop the holdup assay together with other approaches, to reach an increased throughput allowing to evaluate the affinities of at least 10.000 domain-motif interactions a day. This approach will be applied to ii) quantitatively map the entire human PDZ-PBM interactome by identifying all PDZ-PBM interactions and measuring all their binding affinity constants; ii) identify the interactions and the binding affinity constants of the human PDZome vs a panel of viral proteins known to contain C-terminal PBMs. In tight collaboration with experimentalists from the team, the candidate will use bioinformatics tools to design the experiments, treat the large-scale data, analyze the results in the context of pre-existing data from other groups, and set up a website allowing other researchers to visualize the results.
The PhD fellowship is part of the EU-funded project, PDZnet, which is an ambitious inter- and multidisciplinary European Training Network under the H2020 Marie Sk?odowska-Curie Actions (www.pdznet.eu) offering training for 14 PhD fellows. The PDZnet consortium contains 12 different partners in 6 EU countries (Denmark, Sweden, Germany, France, Italy, Portugal). The PDZnet training programme involves a range of network wide training activities.
General job description
Your key tasks as a PhD fellow are to:
-Manage and carry through your research project
-Take PhD courses
-Write scientific articles and your PhD thesis
-Participate in national and international congresses and scientific meetings
-Stay at an external research institution, preferably abroad
-Teach and disseminate your research
-Participate in the undergraduate teaching of students in pharmaceutical sciences
Key criteria for the assessment of applicants
-Professional qualifications relevant to the PhD programme
-Relevant work experience
-The grade point average achieved
-Other professional activities
-The successful applicant is also required to be enterprising and to possess good interpersonal skills.
Compétences & aptitudes souhaitées
The successful candidate must:
-Hold a Master´s degree in a relevant subject area prior to the starting date
-Be fluent in English and have excellent communication skills
-Eager to work in a team and open to experiencing new cultures
We are looking for a highly motivated bioinformatician. She / he should have a MsC in Bioinformatics or a closely related discipline, together with research experience in that field. The candidate should be able to plan and perform programming and bioinformatic tasks in an autonomous manner. She / he should be preferentially interested in applying bioinformatics to the design and analysis of large-scale experimental data, rather than in development of algorithm or software. The candidate should have a basic knowledge in statistics, and have knowledge and interest in protein structure and protein interactomics.
The candidate should have less than 4 years of research experience and must not have resided or carried out his/her main activity in France for more than 12 months during the last 3 years immediately prior to the recruitment.
The successful applicant will be requested to formally apply for enrolment as a PhD student at the University of Strasbourg according to the rules stipulated in the PhD programme at the University (École Doctorale vie et santé, http://ed.vie-sante.unistra.fr/).
How to apply
Applicants are requested to apply electronically by sending to firstname.lastname@example.org a file (pdf format) including:
-Cover letter: Letter stating the interest in and qualifications for the project (max. one page)
-Diploma and transcripts of records: Master´s degree diploma (including grade transcripts for bachelor´s and master´s degrees). Applicants with a Master´s degree from abroad should also enclose a short description of the grading scale used
-Possible publication list
-References and recommendations
Deadline for applications: 30 November 2016.
An answer as to the granting of the fellowship can be expected approx. 4 weeks after application deadline.
Dr Gilles Travé
IGBMC, UMR 7104-U964,
1, rue Laurent Fries, BP 10142,
F-67404 ILLKIRCH Cedex