Lab News

Nicola received his B.Sc in Biology from ETH Zürich in 2021. He is currently enrolled in the Molecular Health Sciences Master´s degree at ETH Zürich and joined the Corn lab mid February 2023. For his Master´s thesis, he is working on the design and set-up of a whole-genome CRISPR screen, aimed at understanding the cellular response towards oxidative damage on lncRNA.

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Naomi received her Bachelor’s degree in Health Science and Technology from ETH Zurich in 2021. Naomi joined the Corn lab in March 2023 as a Master student. For her Master’s thesis, she will analyse the influence of different factors, such as chromatin state or cell type, on off-target and DNA repair outcomes, in a high-throughput manner.

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Mandy was awarded the Innosuisse Innovation grant to fund her translational work on developing gene therapies for hereditary blood diseases. This grant will support the expansion of her team and research.

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Alessandra Albertelli received her Master’s degree in Medical Biotechnology and Molecular Medicine from the University of Milan in 2017. In her Master’s thesis, she focused on long intergenic non-coding RNA in lymphocyte T differentiation. She then spent five years at Heidelberg University as a research assistant and gained competence in confocal microscopy, cell differentiation, genome editing, and protein interaction with DNA and RNA.
Alessandra is curious to learn new techniques and is happy to help the lab with her expertise and passion for her job.
Alessandra joined the Corn lab as Research Technician in January 2023.

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Martina received her MSc in Biology from ETH Zurich in September 2022. She worked in the Corn lab, focusing on the role of the ubiquitin-proteasome system in an autosomal dominant form of cerebral palsy. Martina returned to the Corn lab as a PhD student in December 2022, investigating how chemical modification of the protein backbone affects protein stability. Her research interests include protein homeostasis and functional genomics, as well as the potential application of protein engineering in biotechnology.

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Cas-mediated genome editing technology holds great promise as a curative treatment for a number of genetic diseases. Conventional CRISPR-Cas genome editing induces DNA damage (double stranded DNA breaks) and relies on the cellular DNA repair system to yield the desired repair outcome. This works quite well in cells with a fully operational DNA repair machinery. However, in Fanconi Anemia (FA), a genetic disorder associated with bone marrow failure and cancer predisposition, DNA repair is defective due to the gene mutations causing the disorder. Homology directed repair (HDR)-based editing strategy as an option to correct FA mutations is pretty inefficient (Richardson et al. Nature Genetics 2018). But is it possible to avoid DNA cleavage, and instead use recently developed genome editing systems such as base editing? Can base editing reverse the effects of FA mutations? New work led by a postdoc Erman Karasu (co-corresponding author) and PhD student Sebastian Siegner together with Alexandra Clemens at ETHZ and Laura Ugalde from Paula Rio’s lab shows that this is possible, even in bone marrow stem cells from FA patients.

In this proof-of-concept study, we find that base editing can indeed restore the function of FA bone marrow stem cells. First, the team went through cycles of optimization for the conditions (base editor construct, vector type, guide RNA format, delivery) in cell lines from multiple FA patients. The developed approach effectively corrected FA mutations in both patient-derived cell lines and and bone marrow stem cells from FA patients, leading to restored FANCA expression and functional FA pathway and phenotypic resistance to crosslinking agents.

An obvious question that comes up: how safe is this editing approach? To answer this question, the team predicted possible off-targets and measured the editing outcomes in > 60 sites across multiple base editors. Unintended modifications were detected at a single site with one guide RNA, but a guide RNA targeting the most prevalent FA mutation had no detected off-targets.  Nevertheless, un-biased off- target identification using genome or RNA-sequencing will be the next step in the preclinical validation of base editing as an approach to cure FA.

Altogether, this work highlights base editors as a feasible editing strategy in FA and brings us one step closer to the future clinical implementation of base editing not only in FA, but also in other genetic diseases.

Check out our paper, now out in Nature Communications!

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Are you interested in autophagy of really big things in the cells, such as organelles?  Are you wondering how cutting-edge genetic tools can accelerate your autophagy research? Jin Rui Liang (Amos), a former postdoc, now running his own group at the University of Dundee, wrote a comprehensive review on CRISPR’s impact on autophagy research. Amos outlines the major considerations for CRISPR-based genetic manipulations in autophagy, with a focus on genome-wide screening, as well as various reporter systems for high-throughput autophagy quantification. The article thoroughly summarizes all the relevant info on recently performed autophagy-related screens and their discoveries. Have a CRISPR-view on autophagy, now out in Trends in Cell Biology!

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David received his PhD in Biochemistry from the University of Cambridge in 2022 under the supervision of Prof. Steve Jackson. His work focused on identifying functional genetic interactions within the DNA damage response through CRISPR-Cas9 screens. David joined the Corn Lab as a postdoctoral researcher in October 2022. 

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Jan received his Master´s degree in Immunology from Charles University in 2022, working with Dr. Petr Kašpárek on the role of TNFR1 signalling in the Netherton syndrome. Jan joined the Corn Lab as a Research Assistant in September 2022 and his research interests include regulation of gene expression and synthetic biology, with a special focus on utilizing the CRISPRa/i technologies in therapeutic applications.

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Ana received her PhD in Cancer Biology at the University of Zurich, Switzerland. She carried out her pre-and postdoctoral research studies at the Balgrist University Hospital in Zurich focusing on understanding the molecular mechanisms of bone cancer progression and metastasis, identifying the key regulatory components as well as finding novel innovative therapeutic approaches. Ana joined the Corn lab as a Program Manager in September 2022.

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