Fellows seminar - From molecular scales to cellular scales
This seminar will take place at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) on the Illkirch campus of the University. The IGBMC is one of Europe's leading biomedical research centers, hosting around 700 researchers distributed across around 50 research teams. It was co-founded, with Dino Moras, by the eminent Pierre Chambon (video), who was a founding member of the College of USIAS and currently holds an honorary Chair at USIAS.
Two USIAS projects will be presented at this joint life sciences seminar, by two Fellows located at the IGBMC.
Cooperation of macromolecular machines
Albert Weixlbaumer (2022 Fellow), Team: Regulation of transcription, IGBMC
Genetic information, which is stored in our DNA, needs to be faithfully expressed. This occurs in several steps. First, DNA is transcribed into mRNA (messenger ribonucleic acid) by RNA polymerase. In complex organisms such as humans, the mRNA is processed, and non-coding segments are removed, while the coding segments are ligated together in a process called splicing. Once mRNA is spliced, it can be translated into protein by another macromolecular machine called the ribosome. While conceptually distinct, the machines expressing genetic information do not operate in isolation. Instead, they cooperate and are often physically and kinetically coupled to each other, which enables new functions to emerge. The aim of my lab is to use high-resolution cryo-electron microscopy and understand how those machines operate and how they cooperate.
In the first part of the seminar, I will provide a progress report on the project funded by USIAS, which addresses the coupling of transcription and mRNA splicing. In the second part, I will show results on the cooperation of RNA polymerase with the ribosome.
Self-organisation of organoids
Daniel Riveline (2023 Fellow), Team: Cell physics, IGBMC
Understanding how, out of single cells, functional tissues and organs develop is a major challenge of biology. Recent progress has made it possible to grow organ-like cell assemblies (organoids) from stem cells in vitro. Organoids offer great potential for studying diseases and development in an unprecedented manner. However, in many cases, we do not yet understand how these complex tissues emerge out of progenitor or stem cells. A common feature in the initial growth phase of many organoid systems is the formation of a polarised epithelial cyst with a single or multiple internal apical lumen. This initial transition into an epithelial cyst establishes a tissue template that enables maintenance of progenitor/stem cells (niche) and guides the patterning of differentiated cells into a functional tissue.
Our aim was to understand how the interplay between luminal pressure, proliferation (cell divisions), polarisation (epithelial transition) and differentiation (patterning) leads to self-organisation of this epithelial progenitor template and how this structure facilitates correct patterning into functional organoids. To this end, we systematically controlled and characterised the early growth phase of organoid systems (intestinal, pancreatic and neural tube) and MDCK cysts using imaging, sequencing, numerical simulation, microfabrication, micromanipulations, and mechanical measurements. These integrated results using a common theoretical framework suggest that organoids obey generic rules of self-organisation.
- Read more about Dr. Riveline's USIAS project: Self-organisations in organoids: interplay between cortical activity and cell state.
