Contact
Phone: +49 30 9406-1810
Max-Delbrück-Centrum für Molekulare Medizin (MDC)
Hannoversche Straße 28
10115 Berlin, Deutschland
Hannoversche Straße 28
10115 Berlin, Deutschland
Building 101, Room 1.05
Internal affiliations
Ohler Lab
Computational Regulatory Genomics
Profile
According to current understanding, complexity in higher organisms is not achieved by a more complex repertoire of parts, i. e. genes, but instead by the more complex regulation of the parts.
The expression of genes is tightly controlled on several levels — a large number of protein and RNA factors and DNA and RNA sequence elements enable the precise regulation of interacting gene products. It is a key challenge to decipher these complex networks of players and interactions, and to understand biology via integrated, global approaches.
To this end, our lab develops and applies genomics and computational approaches to understand mechanisms of gene regulation in eukaryotic organisms. Computational biology, and machine learning in particular, has become indispensable to analyze and ultimately make sense of large-scale data sets that look at the phenomenon of gene regulation from different angles.
Our long term goal is to investigate how regulatory networks enable the correct development of complex organisms, with their multitude of cell types that carry out different functions despite the same genome. This will help us to understand the impact of sequence variation on biological functions and disease.
Team
- Former members
- Weichun Huang, joint postdoc with Joe Nevins 2005-2006 (now research staff at NIEHS)
- Dan Mace, CBB PhD '09 (now Microsoft Research, after a postdoc with Bob Waterston, UW)
- Elizabeth Rach, CBB PhD '10 (now at Johnson&Johnson)
- Ken Yokoyama, CBB PhD '10 (advised by Greg Wray, now postdoc in Jian Ma's lab at UIUC)
- Stoyan Georgiev, CBB PhD '11 (now Google Research, after postdoc with Jonathan Pritchard, U Chicago/Stanford)
- Brad Martsberger, joint postdoc with Philip Benfey/DCSB 2009-2011 (now software engineer at Lumere)
- Brad Moore, program developer 2009-2011 (now CBB student)
- Manomani Kumar (Arunachalam), postdoc 2009-2011 (now teaching faculty at Coastal Carolina Univ)
- Alexa Carda, research technician 2009-2012 (now nurse practicioner at Wake Emergency Physicians)
- Molly Megraw, postdoc/K99 fellow 2007-2012 (now Asst Prof at Oregon State University)
- David Corcoran, postdoc 2008-2012 (now head of the Integrative Genomic Analysis Shared Resource at Duke)
- Parawee (Nicky) Lekprasert, CBB PhD '12 (now Officer at the Institute for the Promotion of Teaching Science, Bangkok)
- Bill Majoros, bioinformatician 2006-2013 (now CBB student with Tim Reddy at Duke)
- Iulian Pruteanu Malinici, postdoc 2009-2013 (now at Novartis after a senior postdoc at Harvard)
- Anirudh Natarajan, CBB PhD '14 (now postdoc in Harvey Lodish's lab at at the Whitehead)
- Song Li, postdoc 2010-2014 (now Asst Professor at Virginia Tech)
- Gurkan Yardimci, CBB PhD '14 (now Asst Prof at OHSU after postdoc with Bill Noble at U Washington)
- Samta Malhotra, bioinformatician 2013-2014 (now at the Berlin Institute of Health bioinformatics core)
- Clemens Messerschmidt, bioinformatician 2014-2015 (now at the Berlin Institute of Health bioinformatics core)
- Dina Hafez, Duke CS PhD '15 (now bioinformatician at Natera Inc)
- Sucheta Gokhale, postdoc 2015-2016 (now postdoc at NCL Pune)
- Neelanjan Mukherjee, postdoc 2011-2017 (now Asst Professor at U Colorado)
- Mahmoud Ibrahim, HUB Biology PhD '17 (now at Bayer after postdoc at RWTH Aachen)
- Alina Munteanu, HUB CS PhD '17
- Lorenzo Calviello, HUB Biology '17 (now postdoc with Stephen Floor at UCSF)
- Hans-Hermann Wessels, HUB Biology PhD '18 (now postdoc at the NY Genome Center)
- Aslihan Karabacak Calviello, HUB Biology PhD '19
- Henriette Miko, HUB CS PhD '20 (now at Coditorei)
- Philipp Drewe-Boss, Postdoc 2015-20
Visting students, Master's students, Bachelor students...
- Sarai Cordoba, visiting PhD student 2013 (CRAG Barcelona)
- Merve Oeztuerk, MolMed Charite Berlin Master's 2014 (now grad student at IMB, Mainz)
- Michael Rauer, FU Berlin Bioinformatics Master's 2014 (now Bioinformatics staff member at MPI Freiburg)
- Maja Schuster, U Potsdam Bioinformatics Master's 2015 (now PhD student at MPI Potsdam)
- Lea Heinze, HU Biophysics Bachelor's 2015 (now Master's student at HU)
- Wanja Kassuhn, FU Bioinformatics Bachelor's 2015 (now Master's student at FU)
- Ekaterina Eroshok, MolMed Charite Berlin Master's 2015 (now grad student in this lab)
- Anika Novikov, student research assistant 2016 (now Master's student at FU)
- Camille Schwartz, MolMed Charite Master's 2016 (now Bioniformatics Engineer at NantOmics)
- Julia Philipp, MolMed Charite Master's 2016 (now grad student at UC Santa Cruz)
- Michal Szczesniak, visiting postdoc 2016 (Poznan)
- Eric Lindberg, MolMed Charite Master's 2017 (now PhD student in the Huebner lab, MDC)
- Dominique Sydow, research assistant 2017-8 (now PhD student with Andrea Volkamer at Charite)
- Mariam Hammoud, TU Master's 2018 (now PhD student in the lab with Scott)
- Jan-Martin Romberg, HU Bachelor's 2019
- Christiane Weber, HU Master's 2019
- Henrik Koppke, FU Master's 2020 (now PhD student in the lab with Scott)
- Joel Simoneau, research assistant 2020
- Andreas Drechsel, HU Bachelor's 2020
- Vic-Fabienne Schumann, U Tuebingen Bachelor's 2020
Former undergraduate/rotation students at Duke...
- Jiandong Ding, visiting PhD student 2010 (Fudan University)
- Nicole Varnado, IGSP undergraduate summer fellow 2007 (UT Austin)
- Jimin Choi, CS undergraduate independent research 2007/8
- Aaron Wise, CS undergraduate independent research 2006/8 (now grad student at CMU/UPitt)
- Jonathan Silverman, Bio/Econ, IGSP undergraduate summer fellow 2008
- Weiping Zhang, BME/Econ work/study 2008
- Xuan Ding, BME, HHMI undergraduate summer fellow 2008
- Jeffrey Shen, BME, HHMI undergraduate summer fellow 2009 (now grad student at Harvard)
- Jacob Harer, CS undergraduate independent research 2009/11
- Yiping Wang, CS, HHMI undergraduate research fellow 2009/2011 (now grad student at Cornell)
- Niel Lebeck, CS, independent research 2010/2012
- Hsiang-Yu Yuan, CBB PhD '13 (with Katia Koelle)
- Debbie Winter, CBB PhD '13 (with Terry Furey, then postdoc with Ido Amit at the Weizmann, now Asst Professr at Northwestern)
- Ashlee Benjamin, CBB PhD '13 (With Joe Lucas, now postdoc with Barbara Engelhardt)
- Michael Mayhew, CBB PhD '14 (with Steve Haase, now postdoc at Lawrence Livermore Natl Lab)
- Jason Belsky, CBB PhD '15 (with Dave MacAlpine, now at Omicsoft Inc)
- Jianling Zhong, CBB PhD '15 (with Alex Hartemink, now at LinkedIn)
- Karthik Jayasurya, CBB Master's 2008 (now at Siemens Medical Solutions)
- Jie Xu, CS Master's 2012
Research and Code
We develop and use computational and genomics approaches to understand the biology of gene regulation in eukaryotic organisms.
We are an integrated interdisciplinary lab, whose members aim to understand the gene regulatory code through high throughput experiments and computational approaches. To this end, we want to find out…
- Where are the genetic switches that control the activity of genes at the DNA and RNA level?
- Where are the functionally relevant sequence patterns in those switches?
- What do all the different switches do that control one gene, and how do the patterns and switches work together?
- Can we change or design switches to achieve a defined activity pattern?
We adapt and apply genomics approaches, and collaborate extensively, to obtain new types of molecular data at ever increasing resolution. We develop new computational methods to analyze and integrate new types of data. We design interpretable, predictive machine learning methods — from sparse linear models to deep neural networks — to understand different mechanisms of gene regulation on the DNA and RNA level. These days, our focus is on:
- Explainable artificial intelligence to understand the gene regulatory code, and to quantify the impact of sequence variation
- Generative machine learning to go from decoding to adapting and designing sequences to achieve distinct functions
- Zebrafish and mammalian cell lines as developmental model system that allow for high throughput single cell experiments at different levels of complexity
- Mid- and large-scale perturbation and reporter experiments to dissect distinct aspects of gene regulation
As computational lab, we develop a lot of new software that we make available to the scientific community.
- Older tools and code (prior to ~2019) can be found on the old lab website. Here, you can also find supplemental data and information for older publications.
- Since then, all code can be found via our lab's github repository.
Software
- Legacy tools
Prediction of coding and non-coding genes
Promoter and enhancer analysis
TF target site identification
ChIP/CLIP analysis
miRNA target prediction
Ribosome profiling
Regulatory network topology
Gene expression imaging
Analysis of RNA-binding proteins
Identification of RNA editing events
Best practice tools for sequencing
- GitHub repositories
Promoter and enhancer analysis
TF target site identification
ChIP/CLIP analysis
Ribosome profiling
Analysis of RNA-binding proteins
Machine learning and single cell genomics
Publications
News
Education & Outreach
The lab contributes and participates in university teaching and outreach to a wider community of people interested in science.
Courses
Bachelor's (in German)
Einführung in die Programmierung und Bioinformatik (w/Pawel Romanczuk, summer semester)
Master's (in English)
Computational Analysis and Interpretation of High-throughput Data (w/Laleh Haghverdi and Altuna Akalin, winter semester)
Outreach Activities
Uwe describes the lab's research at Latest Thinking (2018)
A Nature Methods feature on our hunt for meaningful non-protein-coding genes (2018)
Uwe and Philipp led a Meetup at re:publica 2018
Dubravka (Dusa) hosted artist Emilia Tikka to learn about CRISPR-based iPS cells for her piece Aeon (2018). Read the feature in Nature!
Uwe was interviewed for a Nature feature on the research environment in Germany (2019)
Uwe was on stage at Berliner Ensemble's Galileo Galilei to discuss machine learning as part of a "science meets theater" day (2019)
Dubravka and Uwe presented at Children of Doom (2019). Watch the videos here and here!!
The lab was at Lange Nacht der WIssenschaften 2019!
During Berlin Science Week 2020, Karla Stereochemistry performed in the lab -- and Uwe was interviewed for Radio Arty on FluxFM!
Jobs
For available PhD and postdoc positions, please get in touch with Uwe!
Interested in working on a project for your Bachelor or Master's thesis ? Contact Uwe or Scott!