21. Jan. 2020

Gabriel Demo, an experienced scientist in the field of structural biology, mainly protein crystallography and single particle cryo-electron microscopy, joined CEITEC Masaryk University as a new Research Group Leader in January 2020. Gabriel returned to his alma mater after 5 years as a postdoctoral researcher at the University of Massachusetts Medical School in Worcester, United States. His main fields of research interest are bacterial infection, translation control, and RNA biology.

As a new Research Group Leader, Gabriel plans to establish an interdisciplinary research team that will focus on analysing the molecular details of the coupled transcriptional-translational apparatus in bacteria and virus-infected cells. The goal is to set up a team with a unique combination of expertise in transcription, translation, and structural biology. Gabriel has acquired excellent training and experience in numerous techniques and various methodological approaches in chemistry, computational chemistry, biochemistry, molecular biology, and structural biology. This training perfectly leveraged his previous expertise in structural biology, biochemistry and host-pathogen interactions, which was acquired at Masaryk University. Currently, there are no scientific teams in the Czech Republic that focus on cryo-EM studies of transcription and translation. Therefore, the Gabriel Demo Research Group will fill a unique position in the Czech Republic, and will benefit not only from state-of-the-art research facilities and excellent scientific expertise at CEITEC MU, but also from Gabriel´s wide global network of research leaders and experts in the field.  

Meet the Scientist: A Short Interview with Gabriel Demo

What are the scientific questions you wish to address at CEITEC MU?

I am interested in understanding the fundamental mechanism of the transcription-translation coupling in bacteria and in testing the hypothesis that replication of cytoplasmic viruses in eukaryotic cells requires coupled transcription and translation.

In Bacteria and Archaea, newly transcribed RNAs are immediately bound by ribosomes, thus coupling transcription to translation. This contrasts with eukaryotic transcription and translation, which are physically separated by the nuclear envelope. Nevertheless, some double-strand DNA viruses replicate in cytoplasmic factories of infected eukaryotic cells, increasing the possibility that viral transcription might be directly coupled with translation by host ribosomes in vivo.

To understand the mechanism of transcription-translation coupling in bacteria, we will visualise the structures of the coupled complexes using cryo-EM. The state-of-the-art, time-resolved cryo-EM studies will allow us to capture transient structural intermediates of bacterial RNA polymerase and ribosome during transcription-translation coupling. To investigate the transcription-translation coupling of viruses in eukaryotic cells, we will use cryo-electron tomography to visualise the in situ arrangement of ribosomes in the viral factories of infected cells.

These studies will significantly improve our current understanding of gene regulation in bacterial cells and virus-infected mammalian cells, and may point to stress responses in eukaryotes that may challenge the long-standing dogma of functional separation of transcription and translation.

Moreover, high-resolution structures of the coupled complexes will have significant clinical implications for the development of specific drug designs for the inhibition of viral infection in mammalian cells or to treat dysregulated heat shock response, which is associated with numerous pathologies ranging from cancer to neurodegenerative conditions.

Could you please elaborate on your scientific activities at the University of Massachusetts Medical School?

I decided to take a postdoctoral position with Dr. Andrei Korostelev at RNA Therapeutics Institute at the University of Massachusetts Medical School. There, I focused on the study of large macromolecular machines – ribosomes – by applying cryo-electron microscopy. During my postdoctoral stay, I had the opportunity to work on several very interesting projects. Using cryo-EM, I learned how the accuracy of termination in canonical translation or ribosome rescue is achieved and regulated, preventing accumulation of prematurely released proteins, which can be toxic to the living cell. I also contributed to the resolution of structural ensembles of ribosomes, which revealed long-sought after structural differences between the pre-accommodation of cognate and near-cognate tRNAs that elucidate the mechanism of accurate decoding. Moreover, our cryo-EM structures of E. coli RNA polymerase bound to the small ribosomal 30S subunit provided a structural basis for cellular co-localisation of the transcriptional and translational machineries. Therefore, I hope to develop my findings in the field of transcription-translation coupling into a very exciting story, which may reveal a novel regulation pathway.

Why did you choose to join CEITEC MU?

First of all, I think CEITEC MU forms a key part of Masaryk University that is focused on interdisciplinary research in various areas of life sciences. I believe that my team will benefit from the cutting-edge infrastructure available in shared core facilities. Moreover, I received all of my academic degrees (BSc., MSc., and PhD.) at Masaryk University. Therefore, when I had the opportunity to enter a research environment, I chose the one that I consider as my second home. I did not hesitate to join the CEITEC MU research community. CEITEC MU also offers a great, stimulating environment for scientific innovation. In the long run, I hope we will be able to build one of the strongest research focuses on transcription and translation in structural biology in the country.

Do you like living in Brno so far?

As I mentioned before, I consider Brno as my second home because I previously lived in Brno for approximately 10 years. This city always belonged to the students, and it is wonderful to see all of the young people on the streets in Brno. The people here are always direct and very helpful. I also like the historic atmosphere of the city when you enter old town.

What do you value most in the workplace?

At every workplace, I have been eager to find other scientists that are willing to openly share and discuss their ideas. This is very important, because we can push each other towards different and novel directions that we never thought of before. Also, sharing lab space in joint meetings can increase the chance of collaboration and knowledge-sharing between scientific groups. I think that CEITEC MU provides precisely this type of interactive environment.

Could you tell us something interesting or surprising about yourself?

During my scientific career, I lived in various places throughout the world: Brno, Grenoble, London, Washington D.C., and Worcester. However, I loved living in Brno, and am extremely happy to finally be back. I am a passionate hiker, so I am glad to have the opportunity again to enjoy the nature that surrounds Brno.  

Author: Ester Jarour