Previously unimaginable insights into the cell nucleus

The blueprint of life lies carefully folded in the nucleus of the cell. But how do we fit up to two metres of DNA into a cell nucleus that is only six micrometres in diameter? This is an important question because the arrangement of DNA in chromosomes determines which genes are read in gene expression, and how DNA can be repaired and amplified. Prof Christof Gebhardt, scientist at Ulm University's Institute of Biophysics, conducts research into the architecture of chromatic threads. He has been awarded a Starting Grant worth € 1.5 million for his research project by the European Research Council.

Prof Christof Gebhardt
Prof Christof Gebhardt working on a laser measuring equipment

ERC Starting Grant for Project ChromArch

Research Project

Single Molecule Mechanisms of Spatio-Temporal Chromatin Architecture (ChromArch) –  Investigation of molecular mechanisms causing certain chromatin structures in the cell nucleus

Project Leader

Prof Christof Gebhardt

Ammount of Funding

ca. 1.5 million Euro

Programme and Sponsor

Starting Grant of the European Research Council (ERC)

Funding Period

2015 - 2020

Contact

Prof Christof Gebhardt
Institute of Biophysics

Focusing on genome architecture

In the "Spatio-Temporal Chromatin Architecture" (ChromArch) project, the biophysicist studies the spatial and temporal principles that underlie the organisation of chromatin using single molecules in living cells. In this connection, Christof Gebhardt uses reflected light-sheet microscopy (RLSM), a technique that he developed as a post-doc at Harvard University. With this method, scientists can image very thin slices of a cell, and observe the DNA structure and processes deep in the cell. Previously, researchers required numerous cells in order to identify the structure of the genetic material - only to obtain average values. The new microscopy method also has a high degree of sensitivity for fluorescence applications.

Scheme of RLS microscopy
Principal sketch of RLS-Microscopy: a light sheet is directed in such a way that only a very thin layer of the cell will be excited and the fluorescence of single molecules in the cell nucleus is detected.

The art of packaging in chromosomes

Previously unimaginable insights into the cell nucleus have now become possible: Prof Gebhardt will investigate which molecular mechanisms cause the genome to develop certain chromatin structures. For example, loops ensure that enhancers and promoter regions interact. This corresponds to the starting signal of so-called protein biosynthesis, in which a DNA copy (messenger RNA) is translated into amino acids. This is how important building blocks of the body are formed. Altogether, the biophysicist will compare structures that differ only slightly in each cell.

Until 2020 – when the Starting Grant expires – Gebhardt will mainly concentrate on developing the methodology. He will then investigate the arrangement of the genome, which would be the envy of every packaging artist.

Detected fluorescence signal of single molecules in the cell nucleus
Detected fluorescence signal of single molecules in the cell nucleus

Starting support for an early-stage researcher

Early-stage researchers can apply to the European Research Council for a Starting Grant five to seven years after completing their PhD. Their research group should still be at the development stage. A panel of high-level experts decides which projects are eligible for funding; up to € 2 million in funding is awarded over a period of five years. In 2014, 328 projects from the 3,200 applications submitted were successful.

It represents Ulm University’s third Starting Grant: Prof Jens Michaelis, Head of the Institute of Biophysics, and Prof Timo Jacob (Institute of Electrochemistry) were also awarded Starting Grants in the past. “The procedure in Brussels was very time-consuming, and the chances of success were slim,” recollects Prof Gebhardt. Which is why he was all the more delighted about the pledge.