Cercle Gutenberg

Albert Weixlbaumer

Originally from Austria, I studied Molecular Biology at the University of Vienna. During my master thesis in the group of Prof. Renée Schroeder I became fascinated by the versatility and fundamental role of RNA in biology and collaborated with Prof. Eric Westhof at the IBMC. This was my first encounter with research in Strasbourg.

I moved to the UK for my doctoral studies at the University of Cambridge and joined the lab of Dr. Venki Ramakrishnan at the MRC – Laboratory of Molecular Biology. I worked on the mechanism of protein synthesis using X-ray crystallography. I was fortunate because I was part of a team working on a fundamental problem in Biology that culminated in awarding the 2009 Nobel Prize in Chemistry to my doctoral advisor.

After obtaining my PhD I moved to the Rockefeller University in New York, USA to work as a postdoctoral fellow with Prof. Seth A. Darst. I studied the mechanism of RNA transcription, which is the first step in gene expression and therefore plays a critical role in every living cell.

In 2014 I set up my own research lab at the IGBMC in Illkirch and joined Inserm as CRCN. Start-up funding through the ATIP-Avenir program (CNRS/Inserm) as well as funding from the European Union (Marie-Curie Career Integration Grant, ERC Starting Grant) and ANR, allowed me and my team to work on the regulation of transcription by protein and RNA transcription factors as well as the role of supramolecular assemblies involved in gene expression.

Briefly, genes or genetic information is stored in DNA and contains instructions on how to build a protein. Proteins play crucial roles in each organism and have diverse roles. For example, proteins transport oxygen, help fight viruses, digest food to provide energy, or form parts of skin, hair, and finger nails. To access the information stored in a gene, it first needs to be copied into a chemical cousin of DNA, called RNA. This copying process, called transcription, is carried out by a protein enzyme called RNA polymerase. The RNA copy is then used and translated into protein by the ribosome, a large molecular machine composed of both RNA and proteins. These two processes, the transcription of DNA into RNA and the translation of RNA into protein are called gene expression and affect many aspects of biology. Consequently, erroneous gene expression causes many diseases. In my team we want to understand how molecular machines involved in gene expression are regulated and how they work. It is important to realize that these tiny complexes operate by following the laws of chemistry. We visualize them in an electron microscope during different steps of gene expression, which provides a very detailed understanding allowing us to explain how they work on the level of chemistry.

Because our goal is to understand biology on the level of chemistry, I felt particularly honored to receive the Prix Guy Ourisson in 2018, named in honor of chemist Guy Henry Ourisson. Since then, in addition to work on isolated complexes my team also began to study the role of supramolecular assemblies in gene expression. These are composed of two or more molecular machines, which operate in close proximity and modulate each other’s activity. We will continue to use biochemistry and electron microscopy to gain detailed chemical insights and study the next level of structural organization.

 

Selected publications:

  • Webster MW, Takacs M, Zhu C, Vidmar V, Eduljee A, Abdelkareem M, Weixlbaumer A (2020). Structural basis of transcription-translation coupling and collision in bacteria. bioRxiv preprint: doi.org/10.1101/2020.03.01.971028
  • Abdelkareem M, Saint-André C, Takacs M, Papai G, Crucifix C, Guo X, Ortiz J,
  • Weixlbaumer A (2019). Structural Basis of Transcription: RNA Polymerase Backtracking and Its Reactivation. Mol Cell. 75(2), 298-309
  • Guo X, Myasnikov AG, Chen J, Crucifix C, Papai G, Takacs M, Schultz P, Weixlbaumer A (2018). Structural Basis for NusA Stabilized Transcriptional Pausing. Mol Cell 69(5), 816–827 (featured on the cover)
  • Weixlbaumer A, Leon K, Landick R, Darst SA (2013). Structural basis of transcriptional pausing in bacteria. Cell. 152(3), 431-441 (featured on the cover).
  • Weixlbaumer A*, Jin H*, Neubauer C, Voorhees RM, Petry S, Kelley AC, and Ramakrishnan V. (2008). Insights into translational termination from the structure of RF2 bound to the ribosome. Science 322(5903) 953-956. (*these authors contributed equally).