We develop CRISPR-based technologies for high-throughput genome and transcriptome perturbation in microbes, and we apply these technologies in the model Saccharomyces cerevisiae to study complex eukaryotic genetics.
Research in the lab combines development of cutting-edge genome editing technologies with applications that advance our understanding of how genotype determines phenotype. By providing a direct link between sequence and function, at unprecedented scale, these tools allow us to gain principally new insights into how subtle genome variation impacts phenotype and enable massively scaled screens to accelerate construction of designer strains in biotechnology and synthetic biology. We mainly work with the yeast S. cerevisiae, which is a model for many basic processes in humans and other biological systems and an industrially important microbe.
High-throughput CRISPR-based precision genome perturbation
We develop CRISPR technologies for massively parallel precision genome perturbation and direct functional screening in microbes. These build on our platform MAGESTIC (Multiplexed Accurate Genome Editing with Short, Trackable, Integrated Cellular barcodes), which can engineer thousands of defined mutations in parallel in a single test tube. MAGESTIC uses pools of array-synthesized oligos encoding a gRNA and a donor DNA to introduce a designed mutation. Importantly, strains are tagged by DNA barcodes, allowing to efficiently track mutations in cell populations during functional screens and read out mutation identities via barcode sequencing.
Applying precision editing to study how genotype impacts phenotype
We apply our tools to study how genetic differences between individuals impact variation in phenotype, using yeast as a model system. A particular interest lies in studying how mutations that do not alter the amino acid sequence of a protein impact protein expression and function, and how different genetic and environmental contexts alter the impact of a mutation. Using our tools we can also efficiently design, engineer and screen large libraries of mutants for advantageous properties for industrial and medical applications.
Meet the members of the Vonesch Lab!
Sibylle VONESCH (Group Leader)
Sibylle is fascinated by the genomic and phenotypic diversity present in natural populations and loves the power of high-throughput approaches in microbes for understanding generally relevant biological principles. When not in the lab you can find her kitesurfing or running up a mountain.
Postdoc - EMBL Heidelberg, Germany
PhD - ETH Zürich, Switzerland
MSc - University of Zurich, Switzerland
Antoine DELHAYE (Postdoc)
After dabbling in biochemistry for a bit, Antoine switched focus to the intriguing field of systems biology. He loves all things microbiology and is captivated by new technologies. If you ever need to take a break from the lab and have a good night out, he's definitely a partner of choice.
PhD - UCLouvain, Belgium
MSc - Biomolecular and Cellular Engineering, UCLouvain, Belgium
Olivia OZGUC (Research Technician)
Olivia loves the creativity of synthetic biology and is passionate about developing new tools for engineering microbes. Outside of the lab she enjoys art, trying out new baking recipes, and curling up with a good book.
BSc - Biochemistry & Molecular Biology, Oregon State University, USA
Sara BACO (PhD student)
Sara has been cultivating her passion for science since she was a kid and has developed an interest in synthetic biology during her academic journey, which has led her to Belgium. She likes being in touch with nature as well as exploring cities, and after long hours in a labcoat she enjoys a cold beer while searching for a new movie to watch.
MSc - Molecular & Industrial Biotechnology, University of Bologna, Italy
Tamás TROMBITÁS (MSc student)
Tamás is inspired by the potential of genetic engineering and its expected impact on medicine, health and society. He wants to shape the future into a more sustainable and healthy life via the tools of education and science. He likes to be active and to keep himself busy with sports, music and eating delicious food.
MSc student - Cellular & Genetic Engineering, KU Leuven, Belgium
Kristof VAN ASSCHE (MSc student)
Kristof has always had a big interest in genetic engineering and its potential applications in the medical field. During his academic journey, he added to this a newfound love for statistics and is excited to be able to contribute to solving the complex problems in omics in the age of big data. During his free time he likes to be active with urban sports like breakdance or skating & occasionally likes to boulder or hike.
MSc student - Bioinformatics, KU Leuven, Belgium
Raquel MOREIRA DA SILVA (Erasmus intern)
Raquel is fascinated by genetic engineering and its potential, leading her to join the lab. From a young age all 'biothings' have captivated her, which is why you can always find her in nature or near the sea. After hours, she likes to meet friends for a good conversation and tasty dinners.
MSc student - Bioengineering, University of Porto, Portugal
Simon FIESACK (MSc student)
Simon wants to contribute to science through basic research and developing new engineering tools. Besides his interest in science, he loves tasting new things and being in nature. After a long hike, he appreciates a good beer with friends.
MSc student - Cellular & Genetic Engineering, KU Leuven, Belgium
Below is a list of our most recent publications. You can explore the full list of publications on Google Scholar.
*equal contribution #corresponding authors
Ozguc O, Vonesch SC (2022). Protein Expression: Finding abundance regulators. Elife 11 e83907.
Viéitez C, Busby BP, Ochoa D, Mateus A, Memon D, Galardini M, Yildiz U, Trovato M, Jawed A, Geiger AG, Oborska-Oplova M, Potel CM, Vonesch SC, Szu Tu C, Shahraz M, Stein F, Steinmetz LM, Panse VG, Noh KM, Savitski M, Typas A, Beltrao P (2021). High-throughput functional characterization of protein phosphorylation sites in yeast. Nature Biotechnology. https://doi.org/10.1038/s41587-021-01051-x
Vonesch SC#, Li S, Szu Tu C, Hennig BP, Dobrev N, Steinmetz LM# (2020). Fast and inexpensive whole genome sequencing library preparation from intact yeast cells. G3: Genes, Genomes, Genetics 11: jkaa009. https://doi.org/10.1093/g3journal/jkaa009
Vonesch SC#, Bredikhin D, Dobrev N, Villacorta L, Kleinendorst R, Cacace E, Flock J, Frank M, Jung F, Kornienko J, Mitosch K, Osuna-Lopez M, Zimmermann J, Göttig S, Hamprecht A, Kräusslich HG, Knop M, Typas A, Steinmetz LM, Benes V#, Remans K#, Krebs AR# (2020). McQ – an open-source multiplexed SARS-CoV-2 quantification platform. medRXiv. https://doi.org/10.1101/2020.12.02.20242628
Kaminski Strauss S, Schirman D, Jona G, Brooks AN, Kunjapur AM, Nguyen Ba AN, Flint A, Solt A, Mershin A, Dixit A, Yona AH, Csörgő B, Busby BP, Hennig BP, Pál C, Schraivogel D, Schultz D, Wernick DG, Agashe D, Levi D, Zabezhinsky D, Russ D, Sass E, Tamar E, Herz E, Levy ED, Church GM, Yelin I, Nachman I, Gerst JE, Georgeson JM, Adamala KP, Steinmetz LM, Rübsam M, Ralser M, Klutstein M, Desai MM, Walunjkar N, Yin N, Aharon Hefetz N, Jakimo N, Snitser O, Adini O, Kumar P, Soo Hoo Smith R, Zeidan R, Hazan R, Rak R, Kishony R, Johnson S, Nouriel S, Vonesch SC, Foster S, Dagan T, Wein T, Karydis T, Wannier TM, Stiles T, Olin-Sandoval V, Mueller WF, Bar-On YM, Dahan O, Pilpel Y (2019). Evolthon: A community endeavor to evolve lab evolution. PLoS Biology 17(3): e3000182. https://doi.org/10.1371/journal.pbio.3000182
Roy KR*, Smith JD*, Vonesch SC*, Lin G, Szu Tu C, Lederer AR, Chu A, Suresh S, Nguyen M, Horecka J, Tripathi A, Burnett WT, Morgan MA, Schulz J, Orsley KM, Wei W, Aiyar RS, Davis RW, Bankaitis VA, Haber JE, Salit ML, St.Onge RP, Steinmetz LM (2018). Multiplexed precision genome editing with trackable genomic barcodes in yeast. Nature Biotechnology 36, 512–520. https://doi.org/10.1038/nbt.4137
Baliga NS*, Björkegren JLM*, Boeke JD*, Boutros M*, Crawford NPS*, Dudley AM*, Farber CR*, Jones A*, Levey AI*, Lusis AJ*, Mak HC*, Nadeau JH*, Noyes MB*, Petretto E*, Seyfried NT*, Steinmetz LM*, Vonesch SC* (2017). The State of Systems Genetics in 2017. Cell Systems 4: 7-15.
Okada H, Ebhardt A, Vonesch SC, Aebersold R, Hafen E (2016). Proteome-wide association studies identify
biochemical modules associated with a wing size phenotype in Drosophila melanogaster. Nature
Communications 7: 12649. 10.1038/ncomms12649
Vonesch SC, Lamparter D, Mackay TFC, Bergmann S, Hafen E (2016). Genome-wide analysis reveals novel
regulators of growth in Drosophila melanogaster. PLoS Genetics 12(1): e1005616. https://doi.org/10.1371/journal.pgen.1005616