Professor Ferenc Mueller

Image of Ferenc Mueller

Institute of Cancer and Genomic Sciences
Professor in Developmental Genetics

Contact details

Address
Institute of Cancer and Genomic Sciences
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Ferenc  leads a research group in the Institute of Cancer and Genomic Sciences  and as member of the Birmingham Centre for Genome Biology to study encompass transcription regulation in vertebrate development and deciphering the DNA codes of gene expression regulation. he uses zebrafish as a main model system. They collaborate with colleagues in the Medical School and internationally to develop and apply zebrafish models for studying genetic basis of human disorders. Funding for their work comes from H2020 programmes of the European Commission, BBSRC, MRC, British Council, Human Frontier Science Programme and an Investigator award by the Wellcome Trust.

Besides leading a research group, Ferenc teaches in medical genomics and various applied genetics courses and functions as Deputy Director of Research for the College of Medical and Dental Sciences.

Qualifications

  • PhD, Hungarian Academy of Sciences PhD programme, 1997
  • MSc (equivalent 5 year degree), University of Gödöllö, Hungary, Biotechnology, 1993

Biography

Ferenc Mueller joined the University of Birmingham in 2007 as a Senior Lecturer. He became a Reader in 2010 before being awarded his Chair in 2014. Previous to this he was research group leader at the institute of Toxicology and Genetics, Forschungszentrum Karlsruhe (currently Karlsruhe Institute of Technology) in Germany (2001- 2007). He was postdoctoral fellow (EMBO and FRM fellowships) at the IGBMC Strasbourg, France (1997-2001) and research fellow at the University of Southampton, UK (1995-1997).

Teaching

      - Genes to Therapy, 3rd year course, lecturer

Postgraduate supervision

Ferenc is interested in supervising doctoral research students in the following areas:

  • Transcription regulation in embryo development
  • Enhancer-promoter interactions in transcription regulation
  • Imaging of transcription, single cell technologies in detecting gene activity in vivo
  • Epigenetic regulation of transcription in embryo development
  • High throughput screening with zebrafish embryos
  • In vivo modelling of the genetic basis of human disease in zebrafish 

Current PhD students: Ledean Cooper, Fabio D'Orazio, Haseeb Qureshi.

If you are interested in studying any of these subject areas please contact Ferenc on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or 

call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

What can zebrafish tell us about how our genes get switched on?

In our lab we aim to understand the regulatory principles and underlying sequence determinants of transcription regulation in the developing vertebrate embryo. We develop tools for genetic analysis during embryo development, combining genomics and epigenomics while also exploiting the transparency of the fish embryo through visualising gene expression. We collaborate with colleagues in the Medical School to develop and apply zebrafish models for studying genetic basis of human disorders. Funding for our work has been received from H2020 programmes of the European Commission, BBSRC, MRC, British Council, Human Frontier Science Programme and the Wellcome Trust. 

Codes of promoter level transcription regulation in development

The core promoter is a DNA sequence, which is required for recruitment of general transcription factors and provide a platform for Polymerase II transcription. Active promoters can show a diverse range of features and underlying sequence motifs. They serve as an integration point for diverse signals conveyed by cis regulatory elements such as enhancers enabling precise transcription regulation required during vertebrate development. The diversity of core promoter architectures with distinct transcription initiation profiles in vertebrate genomes points at an unexplained regulatory level. Despite of decades of study, we are still strive to clearly define the DNA sequences, whichdetermine where and how Polymerase II initiates transcription.We combine genomics approaches together with functional studies in an embryo model to understand promoter level gene regulation during developmental of the vertebrate embryo. 

Disease-associated cis-regulatory elements in developmental gene regulation

The aberration of transcription regulation of genes can lead to congenital and multifactorial diseases. Large-scale genomics programmes such as ENCODE and FANTOM resulted in prediction of previously unanticipated density of functional elements of the human genome. These predictions raise the need for validation models of predicted functional elements. We are assessing the degree to which zebrafish, with the transparent, externally developing embryo can be used as a surrogate for validating cis-regulatory functions predicted by genome wide assays in mammals and in fish. We are developing methods for functional analysis of predicted cis regulatory elements associated with disease.

Transcription, chromatin dynamics and nuclear organisation in early development

Early development of zebrafish encompassing the maternal to zygotic transition and including zygotic genome activation provides an ideal experimental platform for elucidating the epigenomic features of gene regulation. It allows dissecting the temporal sequence and dynamics of establishing transcriptionally active chromatin state and helps in the identification of determinants required for transcription activation of Polymerase II transcribed genes. The relatively large number of pluripotent cells generated by the fast cell divisions prior to zygotic transcription, in zebrafish, provides sufficient biomass for next generation sequencing technology approaches to establish the temporal dynamics of transcription regulatory events and suggest causative relationship between them. We are annotating epigenetic features, transcriptional start site regions and distal cis-regulatory modules such as enhancers of the developing embryo and its various lineages by CAGE-seq, ChIP-seq ATAC-seq and RNA-seq during development. Analyses of these epigenomic datasets strongly support a model, which suggest that epigenomic premarking mechanisms contribute to developmental gene regulation programme well ahead of commencement of the activation of gene activation and that gametic epigenetic information may contribute to embryonic developmental expression programmes.

Transcription imaging in live embryos

Core promoters and their interaction with cis regulatory modules regulate spatio-temporal dynamics of gene expression and explain not only lineage and tissue specificity but also cell to cell variation of gene expression. To get insight into regulatory principles of transcription dynamics on the single gene and single cell level, we develop transcription imaging tools. Our recent work with a new imaging approach, which we call MOVIE, allows native nascent transcription detection in the transparent zebrafish embryo. Using MOVIE we have monitored the transcription dynamics of the first gene expression in the zebrafish embryo and study the nuclear organisation of the earliest gene expression in unique nuclear compartments.

Biomedical application of the zebrafish model

The Mueller group offers their functional genomic experience with the fish model to collaborate with clinical and non-clinical investigators in their search for the in vivo function of disease causing genes. Based on their experience with embryo phenotyping screening the Mueller group also collaborate with investigators in exploiting zebrafish in developing tools for physiological phenotype detection for screening for drug effects (therapeutic or toxicity) and they seek adapting the embryo phenotyping technologies in non-embryo models such as cancer organoids.

Research Centre: Birmingham Centre for Genome Biology

Find further information on the Mueller group's research on Twitter, Linkedin and ORCID.

Other activities

Ferenc is an Executive Board Member of the Birmingham Centre for Genome Biology.

Coordinator of DANIO-CODE consortium https://www.birmingham.ac.uk/generic/danio-code/index.aspx

https://danio-code.zfin.org

 

 


Publications

Hadzhiev, Y., Qureshi, H., Wheatley, L., Cooper, L. Jasiulewicz, A., Wragg, J.,  Nguyen, H., Poovathumkadavil, D., Conic, S., Bajan, S., Sik, A., Hutvagner, G.,  Tora, L., Gambus, A., Fossey J., and Müller F.  (2019) A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation Nature Communications 10(1):691. doi: 10.1038/s41467-019-08487-5. 

Nepal, C., Hadzhiev, Y., Tarifeño-Saldivia, E., Carninci, P., Andersen, J.B., Peers, B., Lenhard B., and Müller F. (2019) Intertwined canonical and non-canonical initiation in dual promoters are pervasive and differentially regulate Polymerase II transcription preprint: BioRxiv 487496; doi: https://doi.org/10.1101/487496 

Dong, X., Liao, Z., Gritsch,  D., Hadzhiev, Y., Bai, Y., Locascio, J.J., Guennewig, B., Liu, G., Blauwendraat, C., Wang, T., Adler C.H., Frosch, M.P., Nelson, T.P., Rizzu, P., Cooper, A.A. Heutink, P., Beach, G.B, Mattick, J.S., Müller, F., and Scherzer C.R. (2018) An encyclopedia of transcribed elements in human brain dopamine neurons. (2018) Nature Neuroscience (10):1482-1492. doi: 10.1038/s41593-018-0223-0 

Andersson R, Gebhard C, Miguel -Escalada I,  Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA Jensen TH, Suzuki H, Hayashizaki Y, Müller F, Fantom Consortium, Forrest AR, Carninci P, Rehli M and Sandelin A (2014) An atlas of active enhancers across human cell types and tissues. Nature 507(7493):455-61

Haberle V, Li N, Hadzhiev Y, Plessy C, Previti C, Nepal C, Gehrig J, Dong X, Akalin A, Suzuki A-M, van IJcken W, Armant O, Ferg M, Strähle U, Carninci P, Müller F* and Lenhard B (2014) Two independent transcription initiation codes overlap on vertebrate core promoters. Nature 207(7492):381-5
*co-corresponding author

Roberts JA, Miguel-Escalada I, Slovik KJ, Walsh KT, Hadzhiev Y, Sanges R, Stupka E, Balciuniene J, Marsh EK, Balciunas D and Müller F (2014) Targeted transgene integration overcomes variability of position effects in zebrafish. Development 141(3):715-24

Nepal C, Hadzhiev Y, Previti C, Haberle V, Li N, Takahashi H, Suzuki A-M S, Sheng Y, Abdelhamid RA, Anand S, Gehrig J, Akalin A, Kockx CEM, van der Sloot AAJ, van IJcken WFJ, Armant O, Rastegar S, Watson C, Strähle U, Stupka E, Carninci P, Lenhard B and Müller F (2013) Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis. Genome Research 23(11):1938-50

Pasquali L, Gaulton KJ, Rodríguez-Seguí S, Mularoni L, Miquel-Escalada I, Akerman I, Tena JJ, Morán I, Gomez-Marin C, van de Bunt M, Ponsa-Cobas J, Castro N, Nammo T, Cebola I, García-Hurtado J, Maestro MA, Pattou F, Piemonti L, Berney T, Gloyn AL, Ravassard P, Skarmeta JL, Müller F, McCarthy M and Ferrer J (2014) Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nature Genetics 46(2):136-43

Lindeman LC, Andersen IS, Reiner AH, Li N, Aanes H, Ostrup O, Winata C, Mathavan S, Müller F, Aleström P and Collas P (2011) Prepatterning of Developmental Gene Expression by Modified Histones before Zygotic Genome Activation. Dev Cell 21(6):993-1004

Cullinane AR, Straatman-Iwanowska A, Zaucker A, Wakabayashi Y, Bruce CK, Luo G, Rahman F, Gürakan F, Utine E, Ozkan TB, Denecke J, Vukovic J, Di Rocco M, Mandel H, Cangul H, Matthews RP, Thomas SG, Rappoport JZ, Arias IM, Wolburg H, Knisely AS, Kelly DA, Müller F, Maher ER and Gissen P (2010) Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. Nat Genet 42(4):303-12

Gehrig J, Reischl M, Kalmar E, Ferg M, Hadzhiev Y, Zaucker A, Song C, Schindler S, Liebel U and Müller F (2009) Automated high throughput mapping of promoter-enhancer interactions in zebrafish embryos. Nature Methods 6(12):911-6

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