A 3-year post-doctoral position is available to study T cell responses induced by candidate HIV vaccines. The successful applicant will join the team of Lisa Chakrabarti at the Pasteur Institute, and will work in close collaboration with the team of Andrew Griffiths at ESPCI, Paris. The position, funded by ANRS, is available from May 2016.
Patients who spontaneously contain HIV replication in the absence of therapy, called HIV Controllers, show signs of particularly efficient T cell responses. We obtained recent evidence that CD4+ T cells of these rare patients preferentially express a particular set of shared T cell receptors (TCRs) directed to the HIV capsid. We will apply these findings to the field of HIV vaccinology, based on the idea that it would be beneficial to induce the type of T cell response found in HIV Controllers. The main objective will be to devise sensitive and high throughput assays to define the TCR molecular signature induced by candidate HIV vaccines. Systematic comparison with the repertoire of public TCR clonotypes amplified in HIV Controllers will provide a way to rapidly assess the quality of the vaccine response at the molecular level.
The successful candidate will develop microfluidics-based assays to directly couple TCR sequencing with an evaluation of TCR function at the single-cell level. This high-throughput technology will be implemented in collaboration with the group of Andrew Griffiths at ESPCI, who has recently developed a method to analyze millions of single antibody-secreting B cells encapsulated in droplets and to directly clone both BCR chains from cells producing an immunoglobulin of interest. This technology will be transposed to the analysis of T cells, by developing a method to simultaneously sequence both TCR chains from single T cells demonstrating a specific cytokine response. The droplet microfluidicsapproach opens the possibility to map genotype to function for thousands of TCRs per experiment, which should allow unprecedented deep-mining of the TCR repertoire induced by HIV vaccination.
Relevant publications:
– Benati D, Galperin M, Lambotte O, Gras S, Lim A, Mukhopadhyay M, Nouël A, Campbell KA, Lemercier B, Claireaux M, Hendou S, Lechat P, De Truchis P, Boufassa F, Rossjohn J, Delfraissy JF, Arenzana-Seisdedos F, and Chakrabarti LA (2016) Public TCRs confer high-avidity CD4 responses to HIV Controllers. Journal of Clinical Investigation (doi: 10.1172/JCI83792; PMID: 27111229).
– Mazutis L, Gilbert J, Ung WL, Weitz DA, Griffiths AD, Heyman JA (2013) Single-cell analysis and sorting using droplet-based microfluidics. Nature Protocols 8(5):870-91.
Qualifications:
We are looking for a skilled and highly motivated candidate with:
- a PhD in the field of Immunology or Virology,
- research experience in the analysis of TCR responses or in HIV immunology
- a strong motivation to learn and develop microfluidics-based single cell technologies
- a track record of publications in relevant scientific fields
Expertise in cell sorting and NGS will be an asset. The ability to work independently and good communication skills in spoken and written English will be essential.
Application:
Interested candidates should submit their application with a detailed CV, a cover letter detailing skills and motivation, and contact information for 2/3 references to Lisa Chakrabarti, chakra@pasteur.fr
Web site: https://research.pasteur.fr/en/team/viral-pathogenesis/
