Université de Strasbourg

Michael Ryckelynck

Biography

RNA Structure and Reactivity (ARN), Institute for Molecular and Cellular Biology (IBMC), University of Strasbourg and CNRS

Michael Ryckelynck, USIAS Fellow 2018

Dr. Michael Ryckelynck first acquired expertise in RNA biology during  his thesis at Strasbourg’s Louis Pasteur University  that was carried out under the direction of Dr. Richard Giégé (Institute for Molecular and Cellular Biology (IBMC),) and at the end of which he obtained a PhD in Molecular and Cell Biology.

He then joined, in 2006, the group of Professor Andrew Griffiths (Institute of Supramolecular Science and Engineering (ISIS), University of Strasbourg) as a post-doctoral fellow, and significantly contributed to the development of several key components of droplet-based microfluidics as well as the adaptation of the technology to biological applications, especially ultrahigh-throughput screening. In 2007, Michael Ryckelynck was appointed assistant professor of biochemistry at the University of Strasbourg where he initiated a new series of lectures for master students, notably in the area of theoretical and practical microfluidics applied to biology. In 2013, he joined IBMC (UPR 9002-Architecture and Reactivity of RNA), initially as a member of Professor Eric Westhof’s team prior to establishing his own group in 2016. Since then, he heads the team “Digital Biology of RNA”, which is well renowned for its expertise in microfluidic-assisted functional screening of RNA libraries, especially for the discovery of new fluorogenic RNA aptamers. The team has also recently developed several new microfluidic-based single-cell analytical technologies.

In 2015, Michael Ryckelynck received the prize “Les espoirs de l’Université de Strasbourg” awarded by the university to promising young researchers, and was also awarded the Maurice Nicloux Prize in 2017 by the French Society of Biochemistry and Molecular Biology (SFBBM).

Project - TranslatOmiX: massively-parallel characterization of the entire protein synthesis with single-cell resolution

October 2018 – September 2020

Populations made up of isogenic cells (i.e. cells sharing the same genetic information) and growing in the same environment have long been considered as homogeneous groups of cells displaying identical characteristics. This assumption implies that, for instance, every individual of this population would respond in exactly the same manner to a stress-exposure or environmental change. However, several studies have demonstrated that on the contrary, a (sometimes significant)phenotypic variability  does exist from one cell to the other even though they belong to the same clone or cell line. These phenotypic fluctuations can arise, for instance, from natural – stochastic – variation in gene expression or even from slight variations in the microenvironment surrounding the cell. Therefore, despite the fact that the analysis of a large number of cells is required for a good understanding of a biological system, this characterisation must take the cell-to-cell variability into account, which means that analyses with a single-cell resolution are necessary.

Gene expression is orchestrated by regulatory networks that are all more or less interconnected. The proper understanding of a biological system consequently requires analysing it as a whole using global analytical methodologies, or “omics”. These approaches use large populations of cells as starting material and do not, therefore, take cell-to-cell variability into account, even though this variability can be instrumental in cell adaptation as well as various pathologic processes (e.g. infection, cancer…). The main limitation of the current global analytical technologies is linked to the low amount of biological material that can be isolated from a single cell and which is hardly compatible with the laboratory scale reaction volume.

However, the current rise of microfluidics, especially droplet-based microfluidics, allows for a different analytical approach that can be applied at the single cell scale (what is called digital biology) and in a massively parallel manner. Indeed, it is possible to individualise cells into picoliter-sized water-in-oil droplets, in which cells can be lysed – opened up -and the material released (e.g. RNAs, proteins) can be further handled within the droplet while preserving single-cell resolution. This is possible because the oil barrier confines the biological material within the droplets while the small volume of the vessels allows the reagents to be concentrated. This type of technology has recently led to the development of methodologies allowing the analysis of mammalian transcriptome with single-cell resolution. Nevertheless, the simple detection that messenger RNAs are present provides too little information as to whether proteins they encode are also present or not. In this project, we will use droplet-based microfluidics in tandem with innovative chemistry and molecular biology to characterise cell proteome with single-cell resolution and in a massively parallel manner.

Links

Investissements d'Avenir