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All cells of an organism contain the same genome. However, the pattern of gene expression differs considerably between different cell types and also changes over time during development. One way to regulate the expression of genes is achieved by small RNAs that together with Argonaute proteins lead to gene silencing in a process called RNA interference (RNAi). In order to generate a robust RNAi response, the small RNAs must be present in sufficient quantities. How is it decided from which endogenous RNA transcripts small RNAs are produced and how are specific small RNAs then selected for amplification process? In the nuclear RNAi pathway small RNA – Argonaute complexes induce histone methylation and thereby heterochromatin formation. How are the Histone methyltransferases recruited and what are the factors involved in the process? Our research will provide fundamental knowledge of the mechanism of gene silencing and in general on the regulation of gene expression.
Our group uses an integrated structural biology approach, with structural biological techniques forming the core (X-ray crystallography & single-particle electron microscopy) and complemented by biochemical and biophysical approaches. Our research focuses on the mechanistic characterization of protein complexes, which we obtain by two complementary methods. In the bottom-up approach, we produce and purify individual components or protein subcomplexes, which then can be used for the gradual build-up of increasingly larger assemblies. In the top-down approach, a single subunit of a protein complex carries an affinity tag, which allows purifying stable complexes from endogenous sources that can be utilized for structural studies, but for example also for the identification of new interaction partners by mass spectrometry. To complement our biochemical and structural analysis, we perform in vivo experiments together with our collaboration partners.
Sebastian studied Biochemistry at the University of Bayreuth. He received his Ph.D. from Heidelberg University, where he worked on targeting of membrane proteins with Irmi Sinning. During his postdoc with Elena Conti at the MPI of Biochemistry, he combined structural biology and biochemistry to study eukaryotic RNA degradation. From March 2019 he is a group leader at the Max Perutz Labs in Vienna.
Campus Vienna Biocenter 5
1030 Vienna
Room: 1.620
+43-1-4277-74360
PETISCO is essential for piRNA biogenesis in C. elegans. We have determined the structure of several PETISCO submodules that allow us to propose a model for the PETISCO core complex and how it recognizes the piRNA precursor. (Genes & Development 2021)
MTR4 is the central cofactor of the RNA Exosome in the nucleus. In addition to providing helicase activity, MTR4 also acts as a central platform for the recruitment of various RNA-binding proteins like NOP53, AIR2, NVL or NRDE2. They all bind to the KOW domain of MTR4 in a mutually exclusive manner using a conserved motif. (Nature Communications 2019)
Together with the Ketting Lab (IMB Mainz) we have discovered the mysterious enzyme complex, PUCH, which processes the 5' end of piRNA precursors in C. elegans.
PUCH consists of three Schlafen-like domains, which are usually found in endoribonucleases that restrict viral replication. Moreover, PUCH locates to the outer mitochondrial surface, similar to Zucchini in flies and mice. (Nature 2023)
Martin Brehm
PhD Student +43-1-4277-74361
Room: 1.624
Virginia Busetto
PostDoc +43-1-4277-74320
Room: 1.624
Sebastian Falk
Group Leader +43-1-4277-74360
Room: 1.620
Andrej Knarr
Diploma/Master Student +43-1-4277-61656
Room: 1.624
Kevin Alexander Kranz
Diploma/Master Student +43-1-4277-74361
Room: 1.624
Raffael Lichtenberger
Lab Manager +43-1-4277-61656
Room: 1.624
Philipp Mairinger
Diploma/Master Student +43-1-4277-61656
Room: 1.624
Toni Manolova
PhD Student +43-1-4277-61656
Room: 1.624
Aswini Kumar Panda
PhD Student +43-1-4277-52275
Room: 1.321
piRNA processing by a trimeric Schlafen-domain nuclease.
Podvalnaya, Nadezda; Bronkhorst, Alfred W; Lichtenberger, Raffael; Hellmann, Svenja; Nischwitz, Emily; Falk, Torben; Karaulanov, Emil; Butter, Falk; Falk, Sebastian; Ketting, René F
Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans
Perez-Borrajero, Cecilia; Podvalnaya, Nadezda; Holleis, Kay; Lichtenberger, Raffael; Karaulanov, Emil; Simon, Bernd; Basquin, Jérôme; Hennig, Janosch; Ketting, René F; Falk, Sebastian
A ribonuclease III involved in virulence of Mucorales fungi has evolved to cut exclusively single-stranded RNA.
Cánovas-Márquez, José Tomás; Falk, Sebastian; Nicolás, Francisco E; Padmanabhan, Subramanian; Zapata-Pérez, Rubén; Sánchez-Ferrer, Álvaro; Navarro, Eusebio; Garre, Victoriano
The MTR4 helicase recruits nuclear adaptors of the human RNA exosome using distinct arch-interacting motifs
Lingaraju, Mahesh; Johnsen, Dennis; Schlundt, Andreas; Langer, Lukas M.; Basquin, Jérôme; Sattler, Michael; Jensen, Torben Heick; Falk, Sebastian; Conti, Elena
Structure of the nuclear exosome captured on a maturing preribosome.
Schuller, Jan Michael; Falk, Sebastian; Fromm, Lisa; Hurt, Ed; Conti, Elena
Mpp6 Incorporation in the Nuclear Exosome Contributes to RNA Channeling through the Mtr4 Helicase.
Falk, Sebastian; Bonneau, Fabien; Ebert, Judith; Kögel, Alexander; Conti, Elena
Structural insights into the interaction of the nuclear exosome helicase Mtr4 with the preribosomal protein Nop53.
Falk, Sebastian; Tants, Jan-Niklas; Basquin, Jerôme; Thoms, Matthias; Hurt, Ed; Sattler, Michael; Conti, Elena
Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors.
Falk, Sebastian; Finogenova, Ksenia; Melko, Mireille; Benda, Christian; Lykke-Andersen, Søren; Jensen, Torben Heick; Conti, Elena
The molecular architecture of the TRAMP complex reveals the organization and interplay of its two catalytic activities.
Falk, Sebastian; Weir, John R; Hentschel, Jendrik; Reichelt, Peter; Bonneau, Fabien; Conti, Elena
Project title: “Characterization of piRNA processing factors in C. elegans" (I 6110)
doc.funds "RNA@core - Molecular mechanisms in RNA biology" (DOC177)
Coordinator Javier Martinez (Medical Univeristy of Vienna) and Deputy Coordinator: Sebastian Falk (University of Vienna)
Nutrient-regulated control of lysosome function by signaling lipid conversion
14:00 - 15:00
VBC5 Lecture Hall A+B/ZoomShedding Light on the Dark Side of Terrestrial Ecosystems: Assessing Biogeochemical Processes in Soils
12:00 - 13:00 ZoomProtein homeostasis and lifelong cell maintenance
11:00 - 12:00 IMBA/GMI Lecture HallDissecting the turgor sensing mechanisms in the blast fungus Magnaporthe oryzae
11:00 - 12:00 GMI Orange Seminar RoomPikobodies: What does it take to bioengineer NLR immune receptor-nanobody fusions
14:00 - 15:00 GMI Orange Seminar roomWhen all is lost? Measuring historical signals
13:15 - 14:15 UBB - Lecture Hall 1Gene regulatory mechanisms governing human development, evolution and variation
13:00 - 14:00 IMBA/GMI Lecture HallRegulation of Cerebral Cortex Morphogenesis by Migrating Cells
11:00 - 12:00 IMBA/GMI Lecture HallPhage therapy for treating bacterial infections: a double-edged sword
13:30 - 14:30 UBB - Lecture Hall 3Suckers and segments of the octopus arm
11:00 - 12:00 IMBA/GMI Lecture HallUsing the house mouse radiation to study the rapid evolution of genes and genetic processes
13:15 - 14:15 UBB - Lecture Hall 1CRISPR jumps ahead: mechanistic insights into CRISPR-associated transposons
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)SLiMs and SHelMs: Decoding how short linear and helical motifs direct PPP specificity to direct signaling
14:00 - 15:00 MFPL main building, 6th floor SR1/2Title to be announced
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Visualising mitotic chromosomes and nuclear dynamics by correlative light and electron microscopy
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Enigmatic evolutionary origin and multipotency of the neural crest cells - major drivers of vertebrate evolution
13:15 - 14:15 UBB - Lecture Hall 1Engineered nanocarriers for imaging of small proteins by CryoEM
11:00 - 12:00 GMI Orange Seminar RoomBacterial cell envelope homeostasis at the (post)transcriptional level
13:15 - 14:15 UBB - Lecture Hall 1Title to be announced
14:00 - 15:00 VBC5 Lecture Hall A+B/ZoomHydrologic extremes alter mechanisms and pathways of carbon export from mountainous floodplain soils
12:00 - 13:00 UBB - Lecture Hall 1Dissecting post-transcriptional gene expression regulation in humans and viruses
11:00 - 12:00 IMBA/GMI Lecture HallPolyploidy and rediploidisation in stressful times
13:15 - 14:15 UBB - Lecture Hall 1Prdm9 control of meiotic synapsis of homologs in intersubspecific hybrids
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Title to be announced
14:00 - 15:00 VBC5 Lecture Hall A+B/ZoomRNA virus from museum specimens
13:15 - 14:15 UBB - Lecture Hall 1Programmed DNA double-strand breaks during meiosis: Mechanism and evolution
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Title to be announced
11:00 - 12:00