Maria Cristina Gambetta, Associate Professor

Maria Cristina Gambetta received a joint PhD in 2010 from the EMBL in Heidelberg (Germany) and the University of Geneva (Switzerland), and performed post-doctoral research at the Max-Planck Institute of Biochemistry in Martinsried (Germany), studying molecular mechanisms of epigenetic gene silencing by Polycomb transcriptional repressors under the supervision of Jürg Müller. During her post-doctoral training at the EMBL in the laboratory of Eileen Furlong, she studied the role of chromatin architecture in gene activation. She joined the Center for Integrative Genomics in January 2018 as Assistant Professor to study how cells organize the activating and repressive regulatory inputs that are necessary to achieve appropriate gene expression patterns. She was promoted to Associate Professor in August 2023.

For more information please visit: https://gambettalab.org

Research summary

In multicellular organisms, genes are turned ON and OFF in robust spatial and temporal patterns. Regulatory elements that activate or silence gene transcription are inherently promiscuous and can act over long genomic distances. A basic question is how regulatory elements find their target promoters and restrict their activity to their targets.

On the one hand, we study how regulatory crosstalk is prevented. Insulators were discovered in Drosophila and subsequently in various organisms from yeast to humans, as DNA elements that block communication between a regulatory element and a gene promoter when placed in between. In flies and humans, insulators exert their activity by recruiting insulator proteins. We study the biological relevance and molecular mechanisms of insulator proteins.

On the other hand, we study how genes find their appropriate regulatory elements across surprisingly long genomic distances and skip over non-target genes. We address the biological relevance of these interactions by re-wiring them, and we study how they form.

Our studies in flies reveal new evolutionary perspectives into the relevance of 3D genome folding for correctly wiring genes to their regulatory elements.

Masters, PhD and Postdoc positions available; people interested in joining the team are encouraged to write directly to mariacristina.gambetta@unil.ch.

Publications

Mohana G., Dorier J., Li X., Mouginot M., Smith R. C., Malek H., Leleu M., Rodriguez D., Khadka J., Rosa P. et al., (2023). Chromosome-level organization of the regulatory genome in the Drosophila nervous system, Cell 186, 1-19.

Kaushal A., Dorier J., Wang B., Mohana G., Taschner M., Cousin P., Waridel P., Iseli C., Semenova A., Restrepo S. et al., (2022). Essential role of Cp190 in physical and regulatory boundary formation, Science advances, 8 (19).

Kaushal A., Mohana G., Dorier J., Özdemir I., Omer A., Cousin P., Semenova A., Taschner M., Dergai O., Marzetta F. et al., (2021). CTCF loss has limited effects on global genome architecture in Drosophila despite critical regulatory functions. Nature communications, 12 (1)

Gambetta, M.C. & Müller, J. (2015), ‘A critical perspective of the diverse roles of O-GlcNAc transferase in chromatin.’, Chromosoma 124(4), 429–442.

Gambetta, M.C. & Müller J. (2014), ‘O-GlcNAcylation prevents aggregation of the Polycomb group repressor Polyhomeotic.’, Developmental Cell 31(5), 629-639.

Alfieri C. & Gambetta M.C.; Matos R.; Glatt S.; Sehr P.; Fraterman S.; Wilm M.; Müller J.; Müller C.W. (2013), ‘Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements.’, Genes & Development 27(21), 2367-2379.

Gutiérrez, L.; Oktaba, K.; Scheuermann, J.C.; Gambetta, M.C.; Ly-Hartig, N.; Müller, J. (2012), ‘The role of the histone H2A ubiquitinase Sce in Polycomb repression.’, Development 139(1), 117-127.

Gambetta, M.C.; Oktaba, K.; Müller, J. (2009), ‘Essential role of the glycosyltransferase sxc/Ogt in polycomb repression.’, Science 325(5936), 93-96.