Tapahtumakalenteri

Andrea Pauli (Andi) studied biochemistry in Regensburg, Germany, and obtained her Masters in Molecular and Cellular Biology from Heidelberg University, Germany. In 2004, she started her PhD at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria, co-supervised by Kim Nasmyth and Barry Dickson to investigate non-mitotic functions of cohesin using Drosophila as a model organism. In 2006, she moved with Kim Nasmyth to Oxford University, UK, where she obtained her PhD in 2009, providing the first direct evidence that cohesin has essential functions in post-mitotic cells. 

As a postdoc in Alex Schier’s lab at Harvard University, USA, Andi made two key findings that have shaped her research since: first, translation is widespread outside of protein-coding regions in vertebrates; and second, some of the newly discovered translated regions encode functionally important short proteins. 

In 2015, Andi established her own lab at the IMP in Vienna, Austria. The vision of the Pauli lab is to gain mechanistic insights into the egg-to-embryo transition, with a specific focus on the molecular control of fertilization and developmentally programmed dormancy and re-activation. By combining genetic, molecular, cellular, biochemical, structural and genomics approaches, Andi aims to elucidate key mechanisms and regulatory principles at the very beginning of an organism’s life. 

Andi has received numerous honors and awards, including being elected as EMBO YIP (2018) and EMBO member (2021), and having received the FWF START Prize (2017) and an ERC Consolidator grant (2022). In 2022, Andi was promoted to a senior group leader (with tenure) at the IMP. 

Pauli research group, @PauliGroup 

Welcome to this exciting seminar!  

Claudius Kratochwil 

Selected publications 

1. Deneke VE#*, Blaha A#, Lu Y, Draper JM, Phan CS, Panser K, Schleiffer A, Jacob L, Humer T, Stejskal K, Krssakova G, Handler D, Kamoshita M, Vance TDR, Roitinger E, Lee JE, Ikawa M, Pauli A*. A conserved fertilization complex of Izumo1, Spaca6, and Tmem81 mediates sperm-egg interaction in vertebrates. bioRxiv. 2023. https://doi.org/10.1101/2023.07.27.550750. 

This manuscript reports a major breakthrough in the field of fertilization by discovering a trimeric complex on sperm that is predicted to interact with Bouncer on the egg, linking sperm and egg membranes during fertilization. Using AlphaFold predictions we identified and then experimentally confirmed the presence of the trimeric complex on sperm, which is formed by two known essential membrane proteins, Izumo1 and Spaca6, and the previously unknown factor Tmem81, which we show to be essential for fertilization in fish and mice. The egg protein Bouncer is predicted to bind the trimer in the cleft formed by the interacting Izumo1 and Spaca6, thus providing an immediate explanation for the necessity and function of the sperm trimer. Importantly, Alphafold predicts the trimer to be conserved in all vertebrates, while the egg receptor (Bouncer in fish, JUNO in mammals) differs between different species. 

2. Leesch F#, Lorenzo-Orts L#*, Pribitzer C, Grishkovskaya I, Roehsner J, Chugunova A, Matzinger M, Roitinger E, Belačić K, Kandolf S, Lin T-Y, Mechtler K, Meinhart A, Haselbach D*, Pauli A*. A molecular network of conserved factors keeps ribosomes dormant in the egg. Nature. 2023. Jan;613(7945):712-720. doi: 10.1038/s41586-022-05623-y. PMID: 36653451 (bioRxiv https://doi.org/10.1101/2021.11.03.467131) 

This study discovered a developmentally programmed, conserved ribosome state important for ribosome storage and translational repression in the egg. Using cryo-EM structural analyses from zebrafish and Xenopus ribosomes and functional assays in vivo and in vitro, we revealed a dormant ribosome state in which Habp4-eEF2 stabilize ribosome levels and Dap1b-eIF5a repress translation. The newly discovered translational inhibitor Dap1b is inserted into the polypeptide exit tunnel and sufficient to reconstitute the dormant egg ribosome state in vitro. 

3. Stock J, Kazmar T, Schlumm F, Hannezo E*, Pauli A*. A self-generated Toddler gradient guides mesodermal cell migration. Science Advances. 2022. Sep 16;8(37):eadd2488. doi: 10.1126/sciadv.add2488. PMID: 36103529 (bioRxiv https://doi.org/10.1101/2021.12.16.472981) 

This study revealed that a self-generated Toddler gradient guides mesodermal cell migration during gastrulation in zebrafish. We show that Toddler’s receptor, the Apelin receptor, has a dual role during gastrulation by acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Our study uncovers a single receptor-based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex environment of the gastrulating embryo. 

4. Herberg S, Gert KR, Schleiffer A, Pauli A*. The Ly6/uPAR protein Bouncer is required and sufficient for species-specific fertilization. Science. 2018 Sept 7. 361(6406), 1029–1033. http://doi.org/10.1126/science.aat7113. PMID: 30190407. 

This study identified Bouncer, a new essential fertilization factor in fish. We discovered that the previously unannotated protein Bouncer localizes to the egg membrane and is essential for sperm entry. Remarkably, Bouncer is not only required for sperm-egg interaction, but mediates species-specific fertilization between zebrafish and medaka, two evolutionarily distant fish species that cannot normally cross-hybridize. Expressing medaka Bouncer on a zebrafish egg lacking zebrafish Bouncer allows medaka sperm but no longer zebrafish sperm to enter. 

5. Pauli A*, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman S, Mitchell A, Ma J, Dubrulle J, Reyon D, Tsai SQ, Joung JK, Saghatelian A, Schier AF*. Toddler: and embryonic signal that promotes cell movement via Apelin receptors. Science. 2014 Feb 14;343(6172):1248636. doi: 10.1126/science.1248636. PMID: 24407481. 

This study comprised my main postdoctoral work, which predicted hundreds of newly identified translated regions to encode bona fide short proteins. One of these predicted short proteins is 

Toddler, which we discovered to be a novel, essential embryonic signal in zebrafish. We identified Toddler’s receptor and characterized its function during gastrulation where it promotes mesendodermal cell migration. The discovery of Toddler provided direct evidence that the newly identified translated regions can encode functionally important peptides.

6. Pauli A, Althoff F, Oliveira RA, Heidmann S, Schuldiner O, Lehner CF, Dickson BJ, Nasmyth K. Cell-type-specific TEV protease cleavage reveals cohesin functions in Drosophila neurons. Dev Cell. 2008 Feb;14(2):239-51. PMID: 18267092; PMCID: PMC2258333.

This study provided the first direct evidence for functions for cohesin outside its canonical role in sister chromatid cohesion. Using Drosophila as model system, selective elimination of pre-established cohesin complexes in non-proliferating cells with inducible TEV-protease cleavage revealed functions for cohesin in various non-mitotic cell types, including post-mitotic neurons and endocycling larval salivary gland cells.