Postdoctoral fellowship – Deciphering the molecular complexity of derived-products of bacteria (decode)

Keywords: Metabolomic, Ion Mobility,Tandem Mass Spectrometry, Bacteria, Natural products

*DESCRIPTION

Context

Microbial genome sequencing has unveiled numerous cryptic specialized metabolite gene clusters, most of which remain unexpressed under standard cultivation conditions. These clusters are believed to encode a wide variety of biologically active natural products, but their activation often requires specific environmental stimuli. For instance, changes in nutrient availability, co-culturing with competing species, or exposure to signaling molecules can trigger the expression of these latent metabolic pathways.

In addition, the discovery of novel natural products remains challenging due to the chemical and biological diversity of samples. To address this, untargeted metabolomics has emerged as a powerful tool. This approach enables the comprehensive measurement and analysis of all detectable metabolites within a sample, a way for the identification of previously unknown compounds.

Current technologies are in full development to decipher such complex metabolomic samples. Tandem analytical techniques are becoming increasingly common, including hyphenated methods that combine one separation method such as liquid chromatography and a detection system. As a detector, high-resolution mass spectrometry (HRMS) capable of working in tandem mass spectrometry (MS/MS) has emerged as a powerful analytical tool to partly elucidate the structural complexity of bioactive compounds. Indeed, fragmentation data can be used to annotate features by querying natural product databases and searching MS/MS feature similarities. However, the identification confidence of metabolites such as isomers may remain low or even unsuccessful because of the numerous non-elucidated isomers. Recently, the implementation of ion mobility (IM) system on LC-MS/MS adds an unrivalled potential of separation of such compounds as it discriminates their collision cross section value in a specific gas (CCSgaz), an orthogonal feature to LC and MS. This is a novel indicator, linked to the gas phase structure of the metabolites, that improve the identification level of natural compounds.

Objectives & approaches

The aim of the project is to develop a specific workflow on the new LC-IM-MS/MS system of the Université de Lorraine (LC-timsTof Pro 2) to accelerate the discovery of new therapeutic candidates by facilitating comprehensive chemical profiling of microbial strains. As a proof of concept and for methodology development, the project will initially focus on well-characterized compounds produced by Streptomyces ambofaciens before being extended to the discovery of novel bioactive compounds from this strain, especially those involved in an antiproliferative activity observed in specific culture conditions.

Research teams

The post-doctoral fellow will integrate the LCP-A2MC research unit (UR4632 Université de Lorraine). His/her research will be based at Metz (France) and will regularly exchange with the DynAMic Lab (Nancy) for microbial assay and sample preparation. The post-doctoral fellow will be mentored by Prof. Vincent CARRÉ (LCP-A2MC) who is a specialist in developing new bioanalytical and bio-chemistry approaches by high resolution mass spectrometry techniques and Prof. Bertrand AIGLE (DynAMic) who is a specialist in microbiology, genomics and specialized metabolism of Streptomyces.

Equipment

• The LC-IM-HRMS/MS instrument is installed at the MassLor platform (LCP-A2MC, Metz) – Tims-TOF Pro2 (Bruker) with UPLC Elute
• Softwares adapted for data metabolomic monitoring are accessible.
• Strepromyces strains and cell culture room equipment’s are present in the DynAMic Lab.
• Other MS instruments available at the MassLor plateform will also be accessibles (FT-ICR MS Solarix 7T 2xR, Bruker, Ultimate 3000 Velos Pro, Thermoscientific,…).

Selection criteria

Candidate will have received a PhD in Mass Spectrometry for biology purpose. He/She will be familiar with the technique of IMS-MS2 and metabolomic workflow. Applied knowledge in microbial ecology or microbial metabolomics will be a plus. The candidate must have good human skills and be able to write reports and publications in English.

TERMS AND TENURE

This one-year position will be based at the LCP-A2MC, 1 boulevard Arago, 57070 METZ France. The duration can not exceed 12 months.

The target start date for the position is 1st of November 2025, with some flexibility on the exact start date (until January 2026).

HOW TO APPLY

Applicants are requested to submit the following materials:

• A cover letter applying for the position
• Full CV and list of publications
• Academic transcripts (unofficial versions are fine)

Deadline for application is 30th of September 2025. Applicants will be interviewed by an Ad Hoc Commission by middle of October 2025.

Applications are only accepted through email. All document must be sent to:

[email protected]

JOB LOCATION

LCPA2MC, 1 boulevard Arago, 57070 Metz, Lorraine, France

REQUIREMENTS

DOCUMENTS

• Curriculum Vitae – Your most recently updated C.V. including list of publications
  • Cover Letter
  • Statement of Research