Principal Investigator Nicolas Battich
Quantitative Cell Biology
We are interested in the strategies that cells use to control gene expression levels and variability during differentiation. The links between the dynamic nuclear structures and transcriptional changes are a focus of our lab. The compartmentalization of the nucleus into several functional condensates, so-called membrane-less organelles, contributes to transcriptional regulation. We study how different compartments in the nucleus spatially organize the genome and how this impacts gene expression throughout development.
We develop cutting-edge quantitative methods for single-cell genomics and combine them with cellular phenotyping using high-content confocal microscopy. We design data-driven approaches, we build quantitative predictive models and use state-of-the-art machine-learning to gain insights into the cellular processes we study.
- Transcription in single cells
Most cellular processes involve the action of hundreds of different molecular species, and transcription is not an exception. Due to this complexity, many genes are transcribed in a discontinuous stochastic manner in single cells. Periods of active transcription are followed by gaps in which few transcripts are generated. This process is described by the two-state model of transcription. We study how these stochastic dynamics are coordinated at the genome-wide level in the context of nuclear compartmentalization and throughout differentiation.
- Membraneless organelles during differentiation
The organization of the genome into higher-order chromatin structures as well as its spatial organization within the nucleus, for instance the dynamic positioning of genes relative to each other, influences transcriptional activity. Recent evidence suggests that the compartmentalization of the nucleus into functional condensates, so-called membraneless organelles (MLOs), contributes to transcriptional regulation.
Some MLOs form by liquid-liquid phase separation in the cytoplasm and nucleoplasm of eukaryotic cells and have been tightly linked to different aspects of RNA biogenesis and metabolism. In the nucleus, the most prominent MLOs are nucleoli, which are dedicated to the transcription and biogenesis of ribosomal RNA. Nuclear speckles (NSs) were originally linked to mRNA splicing since they were found to be enriched in splicing factors (e.g. SC35), pre-mRNA splicing metabolism and export factors. Recently it has been shown that NSs interact with active genes suggesting they might be hubs for pre-mRNA synthesis as well as metabolism. Transcriptional regulators are also enriched in PML (promyelocytic leukemia) nuclear bodies (PML-NBs). PML-NBs additionally contain proteins involved in DNA damage response and apoptosis, seem to control the balance between cell cycle progression and differentiation.
During differentiation nuclear MLOs are dynamic. One key question to address is the functional link between these dynamics and the changes in the gene regulatory networks and transcriptional output observed as cell differentiate. Are the dynamics of MLO states a consequence of transcription and chromatin organization, or do MLOs actively regulate the temporal dynamics of transcription?
- Our Technologies
Single-cell genomics with temporal and spatial resolution: We develop technologies to measure the temporal and spatial dynamics of transcription using single-cell sequencing platforms and single molecule imaging.
Genetic perturbations: To investigate the function of different genetic elements in driving the structure of the genome and the dynamics of transcription we employ genetic perturbation methods such as CRISPR interference and activation and well as RNAi.
Deep-learning applied to single-cell biology: We are keen in developing and applying deep learning methods to process imaging data sets as well as learning biological meaningful representations of single-cell sequencing data. We are working towards AI methods that extract interpretable parameters from large scale data-sets.
Dr. Nicolas Battich
Principal Investigator, quantitative cell biology lab
Nico Battich began his scientific career in Scotland, where in 2010 he obtained a first-class degree in Molecular and Cellular Biology from the University of Glasgow. He carried out his Ph.D. in Systems Biology at the University of Zurich. Nicolas has been awarded postdoctoral fellowships from the Swiss National Science Foundation and the Human Frontier Science Program to conduct research at the Hubrecht Institute in the Netherlands. He is a group leader at the Helmholtz Pioneer Campus in Munich since August 2022, where he works on the systems biology of stem cell differentiation.
Dr. Nicolas Battich
Positions and Career
2022 - present
Principal Investigator Helmholtz Pioneer Campus, Helmholtz Zentrum München
2016 - 2021
Postdoctoral Fellow at the Hubrecht Institute, Utrecht, NL
2010 - 2016
Ph.D. Researcher at the Institute of Molecular Life Sciences, University of Zurich
2008 - 2009
Master Student at Astra Zeneca, Dept. of Molecular Toxicology, Macclesfield, UK
Internship at the Institute for Atomic and Molecular Physics (AMOLF), Amsterdam
Internship at the Sainsbury Laboratory, John Innes Centre, Norwich, UK
2010 - 2015
Ph.D. in Systems Biology, University of Zurich, Switzerland
Thesis: Origins and control of single-cell transcript heterogeneity
2005 - 2010
M.Sci. with Honors of the First Class in Molecular and Cellular Biology, University of Glasgow, UK.
Honors and Awards
ERC Starting Grant, EU
EMBO workshop on Single Cell Biology Poster Prize, Japan
Human Frontier Science Program Postdoctoral Fellowship
SNSF Early Mobility Postdoctoral Fellowship, Switzerland
Annual Prize of the Faculty of Science for Best Doctoral Thesis, University of Zurich, Switzerland
EMBO Poster Prize, 5th EMBO meeting, Amsterdam, NL
SystemsX Day Poster Prize, Bern, Switzerland
Class Prize Molecular and Cellular Biology, University of Glasgow, UK
Sainsbury Studentship of the Gatsby Foundation, UK
Lorimer Bursary, University of Glasgow, UK
Gatsby Work-Placement Bursary, Gatsby Foundation, UK
Dobbie Smith Prize for Plant Science, Univ. of Glasgow, UK
Invited speaker: Helmholtz Zentrum München, Institute Seminar Series of the Institute of Computational Biology (Munich, Germany)
Poster: EMBO workshop on Single Cell Biology (Tokyo, Japan)
Invited speaker: Small RNA Biology Meeting (Vienna, Austria)
Invited speaker: Single Cell Genomics (Boston, USA)
Invited speaker: France Bio Imaging workshop (Paris, France)
Invited speaker: EMBO conference Cellular Heterogeneity (Heidelberg, Germany)
Invited speaker: Statistical Methods for Post Genomic Data (Munich, Germany)
Invited speaker: EMBO conference “From Functional Genomics to Systems Biology” (Heidelberg, Germany)
Poster: 5th EMBO meeting (Amsterdam, NL)
Battich N*‡⸸, Beumer J, de Barbanson B, Krenning L, Chloé B, Tanenbaum M, Clevers H, van Oudenaarden A.
Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies.
Science 2020 Mar 6;367(6482):1151-1156. doi: 10.1126
Salmén F, De Jonghe J, …, Battich N, et al.
High-throughput total RNA sequencing in single cells using VASA-seq.
Nat Biotechnol. 2022 Jun 27. doi: 10.1038/s41587-022-01361-8.
Stoeger T*, Battich N*, Pelkmans L.
Passive noise filtering by cellular compartmentalization.
Cell 2016 Mar 10;164(6):1151-1161. doi: 10.1016
Battich N*, Stoeger T*, Pelkmans L
Control of transcript variability in single mammalian cells
Cell 2015, DOI:https://doi.org/10.1016
Battich N*, Stoeger T*, Pelkmans L
Image-based transcriptomics in thousands of single human cells at single-molecule resolution.
Nat Methods. 2013 Nov;10(11):1127-33. doi: 10.1038
Helmholtz Pioneer Campus
Helmholtz Zentrum München
Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
Ingolstädter Landstr. 1