Andrea Pauli | |
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Born | 1977 |
Alma mater |
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Awards | |
Scientific career | |
Fields | molecular basis of vertebrate fertilisation |
Institutions | |
Doctoral advisor | Kim Nasmyth |
Other academic advisors | Alexander F. Schier |
Website | www |
Andrea Pauli (born 1977) is a developmental biologist and biochemist studying how the egg transitions into an embryo, and more specifically the molecular mechanisms underlying vertebrate fertilisations, egg dormancy, and subsequent egg activation. [1] Her lab uses zebrafish as the main model organism. [2] Andrea Pauli is a group leader at the Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter in Austria. [3]
Andrea Pauli grew up in Bavaria, Germany. She studied biochemistry at Regensburg University, followed by a master’s in molecular and cellular biology at Heidelberg University. [4] In 2004, she started her doctoral research under the joint supervision of Barry Dickson and Kim Nasmyth at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria. When Nasmyth transferred to the University of Oxford in 2006, Pauli moved with him and obtained her PhD from Oxford in 2009. [5] As a student, she competed twice in the Oxford-Cambridge Women’s Boat Race (2007 and 2008) for Oxford. [6]
Andrea Pauli became a postdoctoral researcher in the lab of Alexander F. Schier at Harvard University in 2009. [4] In 2015, she returned to the IMP to establish her own lab as a group leader. Since 2018, Pauli teaches zebrafish summer courses at the Marine Biological Laboratory in Woods Hole [7] and in 2020, she became the dean of the Vienna Biocenter summer school. [8]
Andrea Pauli's doctoral research focused on cohesin, a protein complex initially known for its essential role in holding sister chromatids together during cell division. Using Drosophila melanogaster as a model system, Pauli showed new cohesin functions in non-proliferating cells. [9] [10] Pauli later turned to zebrafish as model system and to characterising embryonic transcripts, [11] [12] [13] through which she discovered the essential embryonic signal Toddler/Apela/ELABELA, a secreted peptide necessary for mesoderm migration during gastrulation. [13] This demonstrated that newly identified translated regions can encode previously missed yet functionally important small proteins. [14] [15] Research in Pauli’s lab links developmental biology with biochemistry, molecular and cell biology and genomics in order to uncover essential mechanisms underlying the egg-to-embryo transition. Pauli and her lab have discovered mechanisms underlying embryo morphogenesis, fertilisation and egg dormancy. This includes the discovery that Toddler acts as a guidance cue which steers the directional migration of mesodermal cells via a single-receptor-based self-generated Toddler gradient. [16] Focusing on fertilisation, Pauli and her lab identified the egg protein Bouncer as an essential factor for sperm-egg recognition in fish: [17] Bouncer is essential for sperm entry into the egg and sufficient to switch the species-specificity of fertilisation between zebrafish and medaka. Pauli’s lab characterized the functions of Bouncer’s homolog in mammals, SPACA4, [18] and the zebrafish sperm factors Dcst1/2 [19] and Spaca6, [20] which are conserved in mammals and required for fertilisation in vertebrates. Studying the mechanistic basis of dormancy in the egg, Pauli’s lab discovered a developmentally programmed, conserved dormant ribosome state important for ribosome storage and translational repression, which is conserved in zebrafish and Xenopus laevis. [21]
Fertilisation or fertilization, also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a zygote and initiate its development into a new individual organism or offspring. While processes such as insemination or pollination, which happen before the fusion of gametes, are also sometimes informally referred to as fertilisation, these are technically separate processes. The cycle of fertilisation and development of new individuals is called sexual reproduction. During double fertilisation in angiosperms, the haploid male gamete combines with two haploid polar nuclei to form a triploid primary endosperm nucleus by the process of vegetative fertilisation.
Kim Ashley Nasmyth is an English geneticist, the Whitley Professor of Biochemistry at the University of Oxford, a Fellow of Trinity College, Oxford, former scientific director of the Research Institute of Molecular Pathology (IMP), and former head of the Department of Biochemistry, University of Oxford. He is best known for his work on the segregation of chromosomes during cell division.
Separase, also known as separin, is a cysteine protease responsible for triggering anaphase by hydrolysing cohesin, which is the protein responsible for binding sister chromatids during the early stage of anaphase. In humans, separin is encoded by the ESPL1 gene.
SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.
Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.
The development of fishes is unique in some specific aspects compared to the development of other animals.
Nipped-B-like protein (NIPBL), also known as SCC2 or delangin is a protein that in humans is encoded by the NIPBL gene. NIPBL is required for the association of cohesin with DNA and is the major subunit of the cohesin loading complex. Heterozygous mutations in NIPBL account for an estimated 60% of case of Cornelia de Lange Syndrome.
Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the RAD21 gene. RAD21, an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1A, SMC3, and SCC3 [ STAG1 (SA1) and STAG2 (SA2) in multicellular organisms] proteins, involved in sister chromatid cohesion.
Wings apart-like protein homolog (WAPL) is a protein that in humans is encoded by the WAPAL gene. WAPL is a key regulator of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. Cohesin has a ring-like arrangement and it is thought that it associates with the chromosome by entrapping it whether as a loop of DNA, a single strand or a pair of sister chromosomes. WAPL forms a complex with PDS5A or PDS5B and releases cohesin from DNA by opening the interface between SMC3 and RAD21.
Shugoshin 1 or Shugoshin-like 1, is a protein that in humans is encoded by the SGO1 gene.
The Research Institute of Molecular Pathology (IMP) is a biomedical research center, which conducts curiosity-driven basic research in the molecular life sciences.
Angelika Amon was an Austrian American molecular and cell biologist, and the Kathleen and Curtis Marble Professor in Cancer Research at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, United States. Amon's research centered on how chromosomes are regulated, duplicated, and partitioned in the cell cycle. Amon was elected to the American Academy of Arts and Sciences in 2017.
Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the SMC1B gene. SMC proteins engage in chromosome organization and can be broken into 3 groups based on function which are cohesins, condensins, and DNA repair. SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis. SMC1B protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.
Nucleoplasmin, the first identified molecular chaperone is a thermostable acidic protein with a pentameric structure. The protein was first isolated from Xenopus species
Alexander F. Schier is a Professor of Cell Biology and the Director of the Biozentrum University of Basel, Switzerland.
Frank Uhlmann FRS is a group leader at the Francis Crick Institute in London.
Jan-Michael Peters is a cell- and molecular biologist. Since 2013, he is Scientific Director of the Research Institute of Molecular Pathology (IMP) in Vienna.
Alexander Stark is a biochemist and computational biologist working on the regulation of gene expression in development. He is a senior scientist at the Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter and adjunct professor of the Medical University of Vienna.
Antonio Jesus Giraldez is a Spanish developmental biologist and RNA researcher at Yale University School of Medicine, where he serves as chair of the department of genetics and Fergus F. Wallace Professor of Genetics. He is also affiliated with the Yale Cancer Center and the Yale Stem Cell Center.
Julia Anne Horsfield is a New Zealand biochemist and developmental geneticist. She is professor of pathology at the University of Otago and director of Genetics Otago and the Otago Zebrafish Facility.