PhD position (funded by Amidex)

RESEARCHER PROFILE:PhD/R1: First stage Researcher
RESEARCH FIELD(S)1:Therapeutic RNAs, vaccinology,Epitranscriptomics RNA modification
MAIN SUB RESEARCH FIELD OR DISCIPLINES1:Development of New Technologies for the Synthesis of Therapeutic and Vaccine RNAs

JOB /OFFER DESCRIPTION

This PhD project focuses on the design of innovative therapeutic RNAs that closely mimic natural cellular RNAs and is part of a collaborative effort with an industrial partner. The project includes:

1. Directed evolution experiments on enzymes aimed at improving their catalytic properties and generating new tools transferable to industry.
2. Evaluation of the impact of modifications introduced into RNAs (in collaboration with a CIML team), particularly regarding innate immune activation and the effectiveness of the corresponding therapeutic products.

This project, at the interface between academic research and industrial development, offers a multidisciplinary environment integrating structural biology, enzymology, cell biology, and immunology. It will be conducted in close collaboration with a research engineer responsible for developing the necessary methodologies and tools, as well as a PhD student in the final stage of their thesis.

The project aims to develop optimized and engineered polymerases to improve their efficiency and stability in the synthesis of therapeutic and vaccine RNAs, with a particular focus on phage RNA polymerases.

The project relies on engineering polymerase mutants capable of incorporating modified nucleotides and initiating synthesis in the presence of small RNAs carrying cap analogues. Individual mutations have already been identified in different polymerases, and we will combine this information with structural knowledge of polymerases to target critical regions for synthesis initiation.

The host team, recognized for its expertise in viral replication mechanisms, polymerase characterization, and inhibitor identification, has also demonstrated how viruses modify their RNAs via methylation to evade cellular defences.

By combining expertise in polymerases and RNA modification processes (capping and methylation), our strategy is to develop an innovative method capable of significantly improving technologies for synthesizing therapeutic and vaccine RNAs.

TYPE OF CONTRACT:TEMPORARY
JOB STATUS:FULL TIME
HOURS PER WEEK35
APPLICATION DEADLINE:30/11/2025 & TIME 00:00
ENVISAGED STARTING DATE:01/01/2025
ENVISAGED DURATION: 3 years

WORK LOCATION(S):AFMB Lab,Aix-Marseille Université, CNRS, Marseille, France

WHAT WE OFFER:

We are offering a three-year PhD position at the AFMB laboratory, under the supervision of Dr. Étienne Decroly.Orcid:0000-0002-6046-024X, Lab page: [Link®]
The PhD will be carried out at Aix-Marseille University, within the Doctoral School ED 658. https://ecole-doctorale-658.univ-amu.fr/

Additional information: The Euraxess Center of Aix-Marseille Université informs foreign visiting professors, researchers, postdoc and PhD candidates about the administrative steps to be undertaken prior to arrival at AMU and the various practical formalities to be completed once in France: visas and entry requirements, insurance, help finding accommodation, support in opening a bank account, etc. More information onAMU EURAXESS Portal

QUALIFICATIONS, REQUIRED RESEARCH FIELDS, REQUIRED EDUCATION LEVEL, PROFESSIONAL SKILLS

The candidate should hold a Master’s degree (MSc or equivalent) in Molecular Biology, Biochemistry, Structural Biology, or Biotechnology, with a minimum final grade of 12/20 in the Master’s program (M2).

Experience in RNA biology or biochemical and protein purification proteins will be appreciated.

The ideal candidate should:

• Have abackground, biochemistry, or biotechnology.
• Be familiar withtechniques for RNA synthesis, purification, and analysis (e.g.,in vitro transcription, PAGE, HPLC, spectrophotometry).
• Show interest intherapeutic RNA design and production, includingRNA modification and capping strategies.
• Have interest inprotein structural analysis (X-ray crystallography, cryo-EM, or other biophysical methods).
• Be able to use or learncomputational tools for protein and RNA structure prediction, includingAlphaFold and related modelling approaches.

Basic familiarity withbioinformatics tools for RNA and protein sequence analysis.

Soft skills:

• Demonstrate the ability to work independently while contributing effectively to a collaborative research team.
• Possess good communication skills.

REQUESTED DOCUMENTS OF APPLICATION, ELIGIBILITY CRITERIA, SELECTION PROCESS

The candidate should hold a Master’s degree (MSc or equivalent) in Molecular Biology, Biochemistry, Structural Biology, or Biotechnology, with a minimum final grade of 12/20 in the Master’s program (M2). The doctoral school will evaluate its eligibility to the PhD program.

Candidates are invited to send a CV and a cover letter

HOW TO APPLY:[emailprotected]