Postdoctoral Researcher (M/F) in biophysics, biochemistry and microbiology

Job Description

Missions

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the world's deadliest infectious diseases, responsible for over a million deaths annually. The current dogma is that Mtb is transmitted exclusively through coughing. However, recent observations of organisms with morphological and metabolic characteristics of Mtb bacilli in the exhaled breath of TB sufferers challenge this dogma. Moreover, such organisms were even observed in the breath of individuals without any obvious TB symptoms, suggesting these individuals may represent a previously overlooked reservoir capable of spreading Mtb. This highlights the urgent need for innovative strategies to identify individuals at risk of transmitting TB, which may rely on the specific detection of Mtb in the breath.
The DetectTbTransmitters project aims to address this need by identifying specific biomarkers of Mtb bacteria in the breath. The recruited postdoctoral researcher will play a pivotal role in this project, conducting biochemical and biophysical analysis of exhaled breath condensate (EBC) samples collected from individuals with or without a TB diagnosis in a high TB-endemic community. The results generated will aid the development of strategies to detect individuals at risk of spreading Mtb and may help inform actions to manage such persons who are potential TB transmitters.

Activity

Microscopic observation of EBC samples revealed the presence of microorganisms resembling mycobacteria given their morphological features and the metabolic labelling of their cell envelope with a fluorescent precursor to glycolipids in the outer membrane of mycobacteria and other actinomycetales. A key objective of the DetectTbTransmitters project is to identify additional biomarkers indicating the definitive presence of Mtb in EBC samples. This requires a more profound understanding of the physiological characteristics of the Mtb-like organisms in these samples.
To address this, the recruited postdoctoral researcher will employ a sophisticated single-cell atomic force microscopy (AFM) approach to image and force-probe organisms obtained from EBC samples in their native state, that is, without re-culturing. Using this approach, they will generate several datasets that may distinguish Mtb from other microorganisms in EBC. First, combined topographic and nanomechanical imaging will be used to generate nanoscale correlative images of EBC organisms' native surface morphology, stiffness and hydrophobic adhesive properties. Second, AFM probes will be functionalised with receptors (antibodies or lectins) that recognise specific epitopes in Mtb cell envelope molecules and used to force-probe single-molecular interactions at the surfaces of EBC organisms. The data generated will enable characterisation of receptor binding kinetics and affinities for epitopes exposed on single EBC organisms, as well as molecular recognition mapping of the lateral surface distribution of these epitopes. This would provide insight into how the thermodynamics of binding and ligand distribution (density, clustering) at the bacterial surface may be exploited to discriminate between Mtb and non-Mtb organisms.
Furthermore, certain mycobacterial cell-envelope-associated molecules are known to be released into the medium. For example, lipoarabinomannan (LAM), a cell envelope lipoglycan produced by mycobacteria, was previously detected at high levels in EBC from TB patients. Relying on this information and insights obtained from the AFM molecular probing experiments, the recruited candidate will also investigate LAM and, potentially, other Mtb molecules that are in solution in EBC samples using a combination of immunoassays with primary antibodies recognising specific epitopes in Mtb molecules, as well as a combination of nuclear magnetic resonance and mass spectrometry approaches, with the support of specialists in the team.

Your Profil

Skills

The recruited postdoctoral researcher will hold a PhD in biochemistry, biophysics, molecular biology, or a related discipline, with a strong background in at least one of these areas. Experience with biochemical and/or biophysical techniques is required. Expertise in AFM or a demonstrated interest in this technique would be highly advantageous. The candidate should be rigorous, organised, and capable of working both independently and collaboratively within an international consortium. Excellent written and oral communication skills in English are essential. They must be able to design and optimise experimental protocols, analyse and interpret complex data, maintain meticulous laboratory records, and present results effectively to collaborators.

Your Work Environment

The work will take place within the “Immunomodulation by Mycobacterial Lipids & Glycoconjugates” team, led by Jérôme Nigou at the Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS/Université de Toulouse (UMR 5089), Toulouse. Our team focuses on deciphering the molecular and cellular bases of Mycobacterium tuberculosis infection and is involved in various programmes aimed at developing new diagnostic, vaccine, and therapeutic approaches against tuberculosis.
The recruited postdoctoral researcher will work within the DetectTbTransmitters project, funded by the ANRS-MIE and the South African Medical Research Council, which brings together a consortium of two teams from the two countries. The postdoctoral researcher will be based at the IPBS in Toulouse under the supervision of Dr Albertus Viljoen and Dr Jérôme Nigou.

Constraints and risks

Work with Mtb will be conducted in a BSL3 laboratory under strict biosafety protocols. The candidate will be required to complete mandatory safety training and adhere to all established biosafety procedures. AFM experiments will be conducted on formaldehyde-inactivated EBC samples according to standard operating procedures at the IPBS for their safe removal from the BSL3 laboratory for analysis at a lower containment level.

Compensation and benefits

Compensation

between €3,041.28 and €4,216.70 gross per month, depending on experience

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions