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School of Life Sciences

Professor Daniel Hebenstreit

Professor

Email: D.Hebenstreit@warwick.ac.uk 

Phone: 024 765 74457

Office: MB10

Hebenstreit webpage

Research Clusters

Quantiative, Systems & Engineering Biology

Cells & Development

Warwick Centres and GRPs

Warwick Integrative Synthetic Biology Centre

Vacancies and Opportunities

For PhD and postdoctoral opportunities, and interest in potential collaborations, please contact me at the above email address.

Research Interests

My group is working on transcription, the production of RNA, in human cells.

Many mechanistic details of this process remain unclear; it is not well understood why most genes are transcribed at strongly fluctuating rates, producing very unequal RNA numbers in different cells of an otherwise identical population. A reason for this might be the transient or unstable nature of many interactions involved in organizing transcription, which is again incompletely understood. Uncertain also remain the spatial arrangements of the factors involved, in particular how certain locations on DNA can determine the transcription rates of very distant genes.

To investigate these and other questions, we pursue an interdisciplinary approach based on experimental molecular biology and computational analysis of large datasets generated with techniques such as sequencing.

Research: Technical Summary

Transcription is central to all life, but many things remain unclear. In particular in eukaryotes, many contributing factors and mechanistic details have been identified for transcription of mRNAs by RNA polymerase II (Pol2), but a number of phenomena remain enigmatic, including:

  • action-at-a-distance type of regulation of gene expression by enhancers
  • the observation of localized hotspots of transcribing polymerase in the nucleus, known as ‘transcription factories’
  • the natures of the local genic and nuclear environment in terms of topological constraints, dynamic rearrangements of these, and factor composition & turnover
  • origins of stochastic fluctuations in the process of transcription, known as ‘transcriptional bursting’ the ‘pausing’ of polymerase at certain positions in a gene
  • the interplay of transcription and DNA with its attached proteins and the varying post-translational modifications on these (‘chromatin landscape’)

A major challenge is that many of these questions are believed to be connected and difficult to study in a reductionist and/or isolated way.

The overall aim of our research is to provide insights into the mechanisms underlying the above phenomena and the relationships among them in human cells.

We are pursuing an interdisciplinary approach based on genome-wide data accumulation (mostly via next generation sequencing methods) and quantitative analysis and results interpretation (bioinformatics, modelling), accompanied by targeted system perturbations (mostly via dCas9 methodology) and imaging strategies.

Subtopics that we are particularly interested in are (i) polymerase pausing, (ii) liquid-liquid phase separation as a mechanism to spatially arrange factors, (iii) Pol2 positional dynamics, (iv) experimental and computational methods development.

One computational tool we developed is LiBiNorm.

LiBiNorm is a simple command line program that mimics the popular htseq-count software and allows diagnostics, quantification, and removal of global bias that RNA-seq data often are affected by as a result of library preparation protocols.

  • Professor at University of Warwick, Coventry, UK, 2023 - present
  • Reader / Associate Professor at University of Warwick, Coventry, UK, 2020 - 2023
  • Associate Professor at University of Warwick, Coventry, UK, 2017 - 2020
  • Assistant Professor at University of Warwick, Coventry, UK, 2012 - 2017
  • MRC Career Development Fellow at MRC Laboratory of Molecular Biology, Cambridge, UK, 2009 - 2012
  • Post-doctoral fellow at the MRC Laboratory of Molecular Biology, Cambridge, UK, 2007 - 2009
  • BSc in Mathematics, University of Salzburg, Austria, 2007
  • PhD in Genetics, University of Salzburg, Austria, 2005
  • MSc in Genetics, University of Salzburg, Austria, 2000