NCT Data Science Seminar

Das NCT Data Science Seminar ist eine campusweite Initiative, die führende Forscher im Bereich der Datenwissenschaft zusammenbringt, um methodische Fortschritte und medizinische Anwendungen zu diskutieren.

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DKFZ, Communication Center, Lecture Hall

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Abstract

Cell engineering is becoming widely useful for biology (e.g., cells as molecular recorders) and biomedicine (e.g., CAR T cell immunotherapy). Our research combines wet-lab and computational methods for genetic engineering human and mouse cells, programming these cells to execute complex new functions in vitro and in vivo. We further investigate epigenetic mechanisms as mediators of cellular memory and plasticity, which are connecting the developmental history of individual cells to their future potential.

Our research follows three synergistic directions: To map and analyze cell states by multi-omics, single-cell, and spatial profiling (READ), to model regulatory circuitries with deep learning (LEARN), and to build artificial biological programs into cells by genome engineering (WRITE). We develop wet-lab and computational methods in these three directions and apply them to problems in cancer and immunology.

READ: We investigate epigenetic and transcription-regulatory processes underlying the immune system and its diseases (Fortelny et al. 2024 Nature Immunology; Moorlag et al. 2024 Immunity; Krausgruber et al. 2023 Immunity), epigenetic heterogeneity in solid tumors (Klughammer et al. 2018 Nature Medicine; Sheffield et al. 2017 Nature Medicine), structural cells in immune regulation (Krausgruber et al. 2020 Nature), and organoids in the context of Human Cell Atlas (Bock et al. 2021 Nature Biotechnology).

LEARN: We developed “knowledge-primed neural networks” to infer regulatory circuits from single-cell data (Fortelny et al. 2020 Genome Biology), evaluated large language models as biomedical simulators (Schaefer et al. 2024 CBM), integrated time-series analysis with CRISPR screens to establish causality at scale (Traxler et al. 2025 Cell Systems), and established a multimodal embedding model of transcriptomes and text for chat-based analysis of gene expression profiles (Schaefer et al. 2025 Nature Biotechnology).

WRITE: We pursue high-content CRISPR screening as an effective method for functional biology at scale (Bock et al. 2022 Nature Reviews Methods Primers), based on the CROP-seq method for CRISPR screens with single-cell RNA-seq readout (Datlinger et al. 2017 Nature Methods) and the scifi-RNA-seq method cost-effective single-cell RNA-seq in millions of cells (Datlinger et al. 2021 Nature Methods).

Combining these three directions, we developed a platform for systematic optimization of CAR T cells with high-content screens in cell culture and in mouse xenograft models of human cancer. We identified gene knockouts that boost the performance of CAR T cells in these screens, and successfully validated the in vivo efficacy of these CRISPR-boosted CAR T cells in mice (Datlinger et al. 2025 Nature).

In conclusion, the combination of high-throughput profiling (READ), deep neural networks (LEARN), and genome editing at scale (WRITE) enables rapid functional dissection of epigenetic cell states and gene-regulatory networks in human cells, and their rational programming for biological research and for therapy. 

Funding: C.B. is supported by an ERC Consolidator Grant (n° 101001971) of the European Union.

Competing interests: C.B. is a co-founder and scientific advisor of Myllia Biotechnology (CRISPR screening technology and service) and Neurolentech (precision medicine for neurodevelopmental disorders).

Biosketch

Christoph Bock is a Principal Investigator at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Professor of [Bio]Medical Informatics at the Medical University of Vienna. His research combines experimental biology (single-cell sequencing, epigenetics, CRISPR screening, synthetic biology) with computational methods (bioinformatics, machine learning, artificial intelligence) – for cancer, immunology, and precision medicine (https://www.bocklab.org & https://bsky.app/profile/bocklab.bsky.social).

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