People

Dr Patrick Varga Weisz

Lecturer
School of Biological Sciences
Dr Patrick Varga Weisz

Research and professional activities

Research interests

Current Research Interests

My team and I explore how the genome, especially in terms of gene expression, is regulated by its dynamic packaging into chromatin and how this allows stem and progenitor cells, e.g., intestinal stem cells, to respond and to adapt to the environment, for example the presence of the microbiota.

Genome regulation by genome packaging

My lab studies how the packing and organization of the genome in the nucleus of each cell affects biological functions. We focus on the intestinal epithelium, a highly dynamics tissues that continuously regenerates itself. It is also the site where a huge number of microbes live (the microbiota or microbiome) and help us in digestion of food matters. Recently, we have shown how the microbiota affect the genome through a novel modification of the packing material of the genome (link to our paper: http://rdcu.be/EntB). An important level of gene regulation occurs at the packaging of genes into the chromatin superstructure. The first building block of chromatin is the nucleosome, composed of histone proteins around which DNA winds. How gene and genome regulation happens dynamically through chromatin remodeling is of fundamental importance, but still requires much illumination. I have a long standing interest in the biochemistry of nucleosome remodelling factors and their role in maintaining specific chromatin states (Yasui et al., Nature 2002, Collins et al., Nature Genetics, 2002; Poot et al., Nature Cell Biology 2004; Rowbotham et al., Mol Cell 2011; Mermoud et al., Cell Cycle 2012, Durand-Dubief et al., PLoS Genetics, 2013; Sun et al., Nature Medicine 2015). In the last ~ 3 years my lab has moved into the field of chromatin dynamics in the intestinal epithelium and the link between chromatin and cellular metabolism/ tissue homeostasis, in part in collaboration with several groups, such as Marc Veldhoen’s (IMM, Lisbon), Marco Vinolo (UNICAMP, Brazil), Matt Zilbauer (Addenbrooke’s hospital, Cambridge). My lab employs mouse genetics (e.g., using CRISPR/Cas9), intestinal organoid culture, genome-wide chromatin analysis (ChIPseq), transcriptomics, proteomics and in vitro biochemistry to obtain insights into molecular mechanisms in intestinal epigenome regulation and how this is affected by microbial products. Furthermore, in the last 4 years my lab has been involved in a collaborative research program (involving the labs of Peter Fraser, Anne Corcoran, Mikhail Spivakov, Sarah Elderkin) investigating changes in genome regulation and nuclear organization in B cell precursor cells upon ageing in the mouse. We will extend these studies on the effect of inflammation and ageing on intestinal stem cells with emphasis on single cell transcriptomics. A major interest is how defects in epigenetic maintenance mechanisms (epigenetic instability) leads to cellular heterogeneity in ageing, with particular focus on intestinal stem cells in the mouse and human. This will reveal insights into the biology of stem cells under stresses, such as those linked to ageing and inflammation. Research Interests • Link between the microbiota and genome regulation • Chromatin dynamics in intestinal epithelial and stem cells • Chromatin remodeling factors and epigenetic stability • Mechanisms of epigenetic inheritance • Epigenetic stability in aging and disease

Teaching and supervision

  • Human Molecular Genetics (BS320)

  • Research Project in Biomolecular Science (BS831)

Publications

Journals (22)

Varga Weisz, PD., Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.. Nature Communications

Sun, H., Damez-Werno, DM., Scobie, KN., Shao, N-Y., Dias, C., Rabkin, J., Koo, JW., Korb, E., Bagot, RC., Ahn, FH., Cahill, ME., Labonté, B., Mouzon, E., Heller, EA., Cates, H., Golden, SA., Gleason, K., Russo, SJ., Andrews, S., Neve, R., Kennedy, PJ., Maze, I., Dietz, DM., Allis, CD., Turecki, G., Varga-Weisz, P., Tamminga, C., Shen, L. and Nestler, EJ., (2015). ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior. Nature Medicine. 21 (10)

Petrini, E., Baillet, V., Cridge, J., Hogan, CJ., Guillaume, C., Ke, H., Brandetti, E., Walker, S., Koohy, H., Spivakov, M. and Varga-Weisz, P., (2015). A new phosphate-starvation response in fission yeast requires the endocytic function of myosin I. Journal of Cell Science. 128 (20)

Varga-Weisz, PD., (2014). Chromatin remodeling: a collaborative effort. Nature Structural & Molecular Biology. 21 (1)

Mermoud, JE., Rowbotham, SP. and Varga-Weisz, PD., (2011). Keeping chromatin quiet: How nucleosome remodeling restores heterochromatin after replication. Cell Cycle. 10 (23)

Varga-Weisz, PD., (2010). Insights into how chromatin remodeling factors find their target in the nucleus. Proceedings of the National Academy of Sciences. 107 (46)

Hogan, CJ., Aligianni, S., Durand-Dubief, M., Persson, J., Will, WR., Webster, J., Wheeler, L., Mathews, CK., Elderkin, S., Oxley, D., Ekwall, K. and Varga-Weisz, PD., (2010). Fission Yeast Iec1-Ino80-Mediated Nucleosome Eviction Regulates Nucleotide and Phosphate Metabolism. Molecular and Cellular Biology. 30 (3)

Varga-Weisz, PD. and Becker, PB., (2006). Regulation of higher-order chromatin structures by nucleosome-remodelling factors. Current Opinion in Genetics & Development. 16 (2)

Poot, RA., Bozhenok, L., Berg, DLVD., Hawkes, N. and Varga-Weisz, PD., (2005). Chromatin Remodelling by WSTF-ISWI at the Replication Site: Opening a Window of Opportunity for Epigenetic Inheritance?. Cell Cycle. 4 (4)

Kukimoto, I., Elderkin, S., Grimaldi, M., Oelgeschläger, T. and Varga-Weisz, PD., (2004). The Histone-Fold Protein Complex CHRAC-15/17 Enhances Nucleosome Sliding and Assembly Mediated by ACF. Molecular Cell. 13 (2)

Poot, RA., Bozhenok, L., van den Berg, DL., Steffensen, S., Ferreira, F., Grimaldi, M., Gilbert, N., Ferreira, J. and Varga-Weisz, PD., (2004). The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Nature Cell Biology. 6 (12)

Collins, N., Poot, RA., Kukimoto, I., García-Jiménez, C., Dellaire, G. and Varga-Weisz, PD., (2002). An ACF1–ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nature Genetics. 32 (4)

Varga-Weisz, PD. and Dalgaard, JZ., (2002). A mark in the core: Silence no more!. Molecular Cell. 9 (6)

Poot, RA., (2000). HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone-fold proteins. The EMBO Journal. 19 (13)

Varga-Weisz, PD., Bonte, EJ. and Becker, PB., (1999). Analysis of modulators of chromatin structure in Drosophila. Methods in Enzymology. 304

Alexiadis, V., (1998). In vitro chromatin remodelling by chromatin accessibility complex (CHRAC) at the SV40 origin of DNA replication. The EMBO Journal. 17 (12)

Varga-Weisz, PD. and Becker, PB., (1998). Chromatin-remodeling factors: machines that regulate?. Current Opinion in Cell Biology. 10 (3)

Varga-Weisz, PD., Wilm, M., Bonte, E., Dumas, K., Mann, M. and Becker, PB., (1997). Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. Nature. 388 (6642)

Varga-Weisz, PD., Wilm, M., Bonte, E., Dumas, K., Mann, M. and Becker, PB., (1997). Erratum: Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II (Nature (1997) 388 (598-602)). Nature. 389 (6654)

Varga-Weisz, PD. and Becker, PB., (1995). Transcription factor-mediated chromatin remodelling: mechanisms and models. FEBS Letters. 369 (1)

Varga-Weisz, PD., Blank, TA. and Becker, PB., (1995). Energy-dependent chromatin accessibility and nucleosome mobility in a cell-free system. EMBO Journal. 14 (10)

Wall, G., Varga-Weisz, PD., Sandaltzopoulos, R. and Becker, PB., (1995). Chromatin remodeling by GAGA factor and heat shock factor at the hypersensitive Drosophila hsp26 promoter in vitro. EMBO Journal. 14 (8)

Reports and Papers (1)

Varga Weisz, PD., Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases

Contact

patrick.varga-weisz@essex.ac.uk
+44 (0) 1206 872318

Location:

3SW.3.04, Colchester Campus