Prizes

Mateusz MENDEL

The Conserved Role of METTL16 m6A Methyltransferase in Gene Expression Regulation
Director: Ramesh Pillai

Mateusz MENDEL (ex aequo)

The Conserved Role of METTL16 m6A Methyltransferase in Gene Expression Regulation
Director: Ramesh Pillai

Mateusz’ thesis in the lab of Ramesh Pillai focused on how a particular chemical modification of messenger RNA, called N⁶-methyladenosine, controls gene expression. During his thesis, Mateusz looked at several proteins responsible for depositing, reading, and erasing this modification on messenger RNA, using a combination of structural, biochemical, and genetic approaches. His main body of work concerns the methyltransferase METTL16, which he showed to be essential for early embryonic development in mice [1]. In the worm model C. elegans, the homologous enzyme responds to nutritional cues methylating a specific pre-mRNA to regulate its splicing, with the splicing inhibition by N⁶-methyladenosine being also conserved in mammals [2]. Mateusz’ fundamental discoveries bring evidence that RNA modifications can directly affect RNA processing and thus gene expression, in response to environmental cues. 

Mateusz’s thesis work on new layers of gene regulation is honoured with the 2022 Arditi Prize.

Mateusz Mendel defended his thesis in Molecular Biosciences in September 2021 and is presently a Scientist in Lead Discovery at Roche, where he is involved in creating new gene therapy tools and searching for novel inhibitors for non-standard targets.

[1] Mendel, M., et al., Methylation of Structured RNA by the m(6)A Writer METTL16 Is Essential for Mouse Embryonic Development. Mol Cell, 2018. 71(6): p. 986-1000 e11.

[2] Mendel, M., et al., Splice site m(6)A methylation prevents binding of U2AF35 to inhibit RNA splicing. Cell, 2021. 184(12): p. 3125-3142 e25.

Anna-Katharina PFITZNER (ex aequo)

Membrane remodelling by dynamic ESCRT-III polymers
Director: Aurélien Roux

Anna did her PhD in the lab of Aurélien Roux, working on membrane remodelling by the ESCRT-III machinery, an ancient and complex assembly of proteins conserved from Archaea to humans. Since the many ESCRT-III subunits can coalesce into a variety of filaments of different shape and function, it was not known how the dynamic interplay of the subunits could govern membrane fission. During her thesis, Anna used and developed an extraordinarily wide range of biophysical, biochemical, imaging, and structural techniques to reconstitute this protein complex in vitro [1]. Her work uncovered how the ESCRT-III subunits assemble sequentially and drive first extension of tubes and then pinching-off of membrane vesicles [2]. 

The seminal nature of her findings has earned Anna the Birnstiel Award in 2020 and the Prix Schläfli in 2022.

Anna-Katharina Pfitzner defended her thesis in Molecular Biosciences in October 2021 and is currently an EMBO postdoctoral fellow in the lab of Tom Rapoport at Harvard Medical School, where she focuses on how proteins and lipids interact on a molecular and mechanistic level, and how transmembrane proteins distort the lipid order within biological membranes.

[1] Pfitzner, A.K., et al., An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission. Cell, 2020. 182(5): p. 1140-1155 e18.

[2] Pfitzner, A.K., J. Moser von Filseck, and A. Roux, Principles of membrane remodeling by dynamic ESCRT-III polymers. Trends Cell Biol, 2021. 31(10): p. 856-868.