Application Deadline : 16 February 2023
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General information
Reference : UPR9002-MICRYC-010
Nombre de Postes : 1
Workplace : STRASBOURG
Date of publication : Thursday, January 26, 2023
Scientific Responsible name : Michael RYCKELYNCK
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 May 2023
Proportion of work : Full time
Remuneration : 1700 € net
Description of the thesis topic
Aptamers (i.e., single stranded nucleic acids adopting a 3D structure allowing them to specifically interact with a target molecule) and ribozymes (nucleic acids endowed with a catalytic function) represent a class of nucleic with growing interest in bioengineering, biomedical and even industrial fields. Lots of such natural and synthetic nucleic acids have been described over the past decades, all being usually functional in water-based environment.
In this project, we will explore a new generation of aptamers and ribozymes adapted to work in non-conventional solvents where water will be exchanged for ionic liquids. To reach this goal, mutant libraries will be functionally screened using droplet-based microfluidics, a technology routinely used by the team. This technology consists in encapsulating biological reactions (e.g., PCR amplification, in vitro transcription, enzyme activity assay…) within picoliter (10E-12 liter) volume water-in-oil droplets produced and manipulated at rates of several thousand per second. All these manipulations are usually performed in water-based media, but one can anticipate that exchanging water for a non-conventional solvent should impact liquid behavior, so the ability to control droplet production and circulation with the devices. Therefore, a first step of the PhD work will consist in adjusting the design of the microfluidic devices to optimize the production and the manipulation of non-aqueous droplets. Then, these devices will be exploited to isolate optimized aptamers/ribozymes and identify most interesting molecules through sequence analysis (high-throughput sequencing in tandem with bioinformatics). Upon characterization, the newly isolated molecules will be transfer to partners where they will serve for various industrial applications.
Work Context
The thesis work will be carried out in the team ” Digital Biology of RNA” headed by Michael RYCKELYNCK and hosted in the CNRS unit ” Architecture et Réactivité de l’ARN ” (Institut de Biologie Moléculaire et Cellulaire, Strasbourg). The team has a unique and internationally recognized expertise in the development and use of droplet microfluidics for the study of nucleic acids (especially RNA), in particular the development, by directed evolution, of fluorogenic RNA aptamers of biotechnological interest, and more recently for applications in microbiology. The team is currently composed of two professors-researchers, one post-doctoral researcher, five PhD students and three engineers.
This PhD project is part of a larger and more ambitious project that received the financial support from the European Innovation Council (EIC) and will involve 8 partners worldwide. We are looking for a highly motivated student with both excellent scientific and soft skills. We are more specifically looking for a candidate with strong background in molecular biology and an interest in technological development. Skills in programming (Python or R) will be a plus but are not mandatory. This PhD contract will be funded for 3 years starting from May 2023.
The PhD student will have access to all the equipment, infrastructure and expertise necessary for the successful completion of the thesis project.
In addition to an informal daily follow-up of the thesis work, weekly meetings will be organized with the thesis director and several project follow-up meetings will also be organized within the consortium. The student will therefore participate to the different consortium meeting organized that will take place in the different partner countries across Europe.
For more information on the team and its activities, please visit the website:
https://ibmc.cnrs.fr/en/laboratoire/arn-en/equipes/biologie-digitale-de-larn/
Constraints and risks
There are no particular risks or constraints associated with this position. The personnel will nevertheless be made aware of and trained on the risks inherent to his/her work environment.