Dr Patrick Varga Weisz
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Email
patrick.varga-weisz@essex.ac.uk -
Telephone
+44 (0) 1206 872318
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Location
3SW.3.04, Colchester Campus
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
Current teaching responsibilities
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Transferable Skills in Life Sciences (BS143)
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Medical Genetics (BS220)
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Genome Science (BS222)
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Research Project in Biomedical Science (BS831)
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Gene Technology and Synthetic Biology (BS934)
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Biomedical Science: Practice and Employability (BS214)
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Research Project in Life Sciences (BS832)
Current supervision
Previous supervision
Degree subject: Biological Sciences
Degree type: Doctor of Philosophy
Awarded date: 19/6/2023
Degree subject: Biological Sciences
Degree type: Master of Science (by Dissertation)
Awarded date: 15/1/2021
Publications
Publications (1)
Puig-Barbe, A., Dettmann, S., Nirello, VD., Azami, S., Edgar, BA., Varga-Weisz, P., Korzelius, J. and de Navascués, J., Homo- and heterodimerization of bHLH transcription factors balance stemness with bipotential differentiation in theDrosophilagut
Journal articles (54)
Corrêa, RO., Castro, PR., Fachi, JL., Nirello, VD., El-Sahhar, S., Imada, S., Pereira, GV., Pral, LP., Araújo, NVP., Fernandes, MF., Matheus, VA., de Souza Felipe, J., dos Santos Pereira Gomes, AB., de Oliveira, S., de Rezende Rodovalho, V., de Oliveira, SRM., de Assis, HC., Oliveira, SC., Dos Santos Martins, F., Martens, E., Colonna, M., Varga-Weisz, P. and Vinolo, MAR., (2023). Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium. Microbiome. 11 (1), 90-
Bannister, AJ., Schneider, R. and Varga-Weisz, P., (2023). Editorial: Colyn Crane-Robinson (1935–2023). Nucleic Acids Research. 51 (15), 7709-7713
Nirello, VD., Rodrigues de Paula, D., Araújo, NVP. and Varga-Weisz, PD., (2022). Does chromatin function as a metabolite reservoir?. Trends in Biochemical Sciences. 47 (9), 732-735
Mukherjee, D., Chora, ÂF., Lone, J-C., Ramiro, RS., Blankenhaus, B., Serre, K., Ramirez, M., Gordo, I., Veldhoen, M., Varga-Weisz, P. and Mota, MM., (2022). Host lung microbiota promotes malaria-associated acute respiratory distress syndrome. Nature Communications. 13 (1)
Varga Weisz, P. and Fellows, R., (2020). Chromatin dynamics and histone modifications in the intestinal microbiota-host crosstalk. Molecular Metabolism. 38, 100925-100925
Kazakevych, J., Denizot, J., Liebert, A., Portovedo, M., Mosavie, M., Jain, P., Stellato, C., Fraser, C., Corrêa, RO., Célestine, M., Mattiuz, R., Okkenhaug, H., Miller, JR., Vinolo, MAR., Veldhoen, M. and Varga Weisz, P., (2020). Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium. Genome Biology. 21 (1), 64-
Fachi, JL., Felipe, JDS., Pral, LP., da Silva, BK., Corrêa, RO., de Andrade, MCP., da Fonseca, DM., Basso, PJ., Câmara, NOS., de Sales e Souza, ÉL., dos Santos Martins, F., Guima, SES., Thomas, AM., Setubal, JC., Magalhães, YT., Forti, FL., Candreva, T., Rodrigues, HG., de Jesus, MB., Consonni, SR., Farias, ADS., Varga Weisz, P. and Vinolo, MAR., (2019). Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. Cell Reports. 27 (3), 750-761.e7
Kazakevych, J., Stoyanova, E., Liebert, A. and Varga Weisz, P., (2019). Transcriptome analysis identifies a robust gene expression program in the mouse intestinal epithelium on aging. Scientific Reports. 9 (1), 10410-
Rodrigues, C., Pattabiraman, C., Vijaykumar, A., Arora, R., Narayana, SM., Kumar, RV., Notani, D., Varga-Weisz, P. and Krishna, S., (2019). A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells. Experimental Cell Research. 378 (2), 206-216
Fellows, R., Denizot, J., Stellato, C., Cuomo, A., Jain, P., Stoyanova, E., Balázsi, S., Hajnády, Z., Liebert, A., Kazakevych, J., Blackburn, H., Corrêa, RO., Fachi, JL., Sato, FT., Ribeiro, WR., Ferreira, CM., Perée, H., Spagnuolo, M., Mattiuz, R., Matolcsi, C., Guedes, J., Clark, J., Veldhoen, M., Bonaldi, T., Vinolo, MAR. and Varga Weisz, PD., (2018). Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nature Communications. 9 (1), 105-
Koohy, H., Bolland, DJ., Matheson, LS., Schoenfelder, S., Stellato, C., Dimond, A., Várnai, C., Chovanec, P., Chessa, T., Denizot, J., Garcia, RM., Wingett, SW., Freire-Pritchett, P., Nagano, T., Hawkins, P., Stephens, L., Elderkin, S., Spivakov, M., Fraser, P., Corcoran, AE. and Varga-Weisz, PD., (2018). Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells. Genome Biology. 19 (1), 126-
Fellows, R. and Varga Weisz, P., (2018). In vitro Enzymatic Assays of Histone Decrotonylation on Recombinant Histones. Bio-protocol. 8 (14), e2924-
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), 1146-1153
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), 3707-3713
Varga-Weisz, PD., (2014). Chromatin remodeling: a collaborative effort. Nature Structural & Molecular Biology. 21 (1), 14-16
Durand-Dubief, M., Will, WR., Petrini, E., Theodorou, D., Harris, RR., Crawford, MR., Paszkiewicz, K., Krueger, F., Correra, RM., Vetter, AT., Miller, JR., Kent, NA. and Varga-Weisz, P., (2012). SWI/SNF-Like Chromatin Remodeling Factor Fun30 Supports Point Centromere Function in S. cerevisiae. PLoS Genetics. 8 (9), e1002974-e1002974
Mermoud, JE., Rowbotham, SP. and Varga-Weisz, PD., (2011). Keeping chromatin quiet. Cell Cycle. 10 (23), 4017-4025
Rowbotham, SP., Barki, L., Neves-Costa, A., Santos, F., Dean, W., Hawkes, N., Choudhary, P., Will, WR., Webster, J., Oxley, D., Green, CM., Varga-Weisz, P. and Mermoud, JE., (2011). Maintenance of Silent Chromatin through Replication Requires SWI/SNF-like Chromatin Remodeler SMARCAD1. Molecular Cell. 42 (3), 285-296
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), 19611-19612
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), 657-674
Neves-Costa, A., Will, WR., Vetter, AT., Miller, JR. and Varga-Weisz, P., (2009). The SNF2-Family Member Fun30 Promotes Gene Silencing in Heterochromatic Loci. PLoS ONE. 4 (12), e8111-e8111
Choudhary, P. and Varga-Weisz, P., (2007). ATP-dependent chromatin remodelling: action and reaction.. Sub-cellular biochemistry. 41, 29-43
Hogan, C. and Varga-Weisz, P., (2007). The regulation of ATP-dependent nucleosome remodelling factors. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 618 (1-2), 41-51
Varga-Weisz, PD. and Becker, PB., (2006). Regulation of higher-order chromatin structures by nucleosome-remodelling factors. Current Opinion in Genetics & Development. 16 (2), 151-156
Aligianni, S. and Varga-Weisz, P., (2006). Chromatin-remodelling factors and the maintenance of transcriptional states through DNA replication. Biochemical Society Symposia. 73 (73), 97-108
Poot, RA., Bozhenok, L., Berg, DLCVD., 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), 543-546
Varga-Weisz, P., (2005). Chromatin Remodeling Factors and DNA Replication. Progress in molecular and subcellular biology. 38, 1-30
Hawkes, NA. and Varga-Weisz, P., (2005). Transcription regulation: no holy grail, but many treasures. Genome Biology. 6 (7), 334-334
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), 265-277
Poot, RA., Bozhenok, L., van den Berg, DLC., 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), 1236-1244
Varga-Weisz, PD. and Dalgaard, JZ., (2002). A Mark in the Core. Molecular Cell. 9 (6), 1154-1156
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), 627-632
Yasui, D., Miyano, M., Cai, S., Varga-Weisz, P. and Kohwi-Shigematsu, T., (2002). SATB1 targets chromatin remodelling to regulate genes over long distances. Nature. 419 (6907), 641-645
Bozhenok, L., (2002). WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci. The EMBO Journal. 21 (9), 2231-2241
Eberharter, A., (2001). Acf1, the largest subunit of CHRAC, regulates ISWI-induced nucleosome remodelling. The EMBO Journal. 20 (14), 3781-3788
Varga-Weisz, P., (2001). ATP-dependent chromatin remodeling factors: Nucleosome shufflers with many missions. Oncogene. 20 (24), 3076-3085
Poot, RA., (2000). HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone-fold proteins. The EMBO Journal. 19 (13), 3377-3387
Corona, DFV., (2000). Two histone fold proteins, CHRAC-14 and CHRAC-16, are developmentally regulated subunits of chromatin accessibility complex (CHRAC). The EMBO Journal. 19 (12), 3049-3059
Varga-Weisz, PD., Bonte, EJ. and Becker, PB., (1999). Analysis of modulators of chromatin structure in Drosophila. Methods in Enzymology. 304, 742-757
Alexiadis, V., (1998). In vitro chromatin remodelling by chromatin accessibility complex (CHRAC) at the SV40 origin of DNA replication. The EMBO Journal. 17 (12), 3428-3438
Varga-Weisz, PD. and Becker, PB., (1998). Chromatin-remodeling factors: machines that regulate?. Current Opinion in Cell Biology. 10 (3), 346-353
Miller, KI., Cuff, ME., Lang, WF., Varga-Weisz, P., Field, KG. and van Holde, KE., (1998). Sequence of the Octopus dofleini hemocyanin subunit: structural and evolutionary implications. Journal of Molecular Biology. 278 (4), 827-842
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. 389 (6654), 1003-1003
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), 598-602
Ivanchenko, M., Zlatanova, J., Varga-Weisz, P., Hassan, A. and van Holde, K., (1996). Linker histones affect patterns of digestion of supercoiled plasmids by single-strand-specific nucleases.. Proceedings of the National Academy of Sciences. 93 (14), 6970-6974
Varga-Weisz, PD., Blank, TA. and Becker, PB., (1995). Energy-dependent chromatin accessibility and nucleosome mobility in a cell-free system.. The EMBO Journal. 14 (10), 2209-2216
Varga-Weisz, PD. and Becker, PB., (1995). Transcription factor‐mediated chromatin remodelling: mechanisms and models. FEBS Letters. 369 (1), 118-121
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.. The EMBO Journal. 14 (8), 1727-1736
Vargaweisz, P., Vanholde, K. and Zlatanova, J., (1994). Competition between Linker Histones and HMG1 for Binding to Four-Way Junction DNA: Implications for Transcription. Biochemical and Biophysical Research Communications. 203 (3), 1904-1911
Varga-Weisz, P., Zlatanova, J., Leuba, SH., Schroth, GP. and van Holde, K., (1994). Binding of histones H1 and H5 and their globular domains to four-way junction DNA.. Proceedings of the National Academy of Sciences. 91 (9), 3525-3529
Weisz, PD. and Barnes, DW., (1993). Characterization of human plasma growth inhibitory activity on serum-free mouse embryo cells.. In vitro cellular & developmental biology. Animal. 29A (6), 512-516
Weisz, PDV. and Barnes, DW., (1993). Characterization of human plasma growth inhibitory activity on serum-free mouse embryo cells. In Vitro Cellular & Developmental Biology - Animal. 29 (6), 512-516
Weisz, PV., Solem, M. and Barnes, D., (1993). Expression of a TGFβ regulated, brain-specific mRNA in serum-free mouse embryo (SFME) cells. Neuroscience Letters. 154 (1-2), 153-156
Varga-Weisz, P., van Holde, K. and Zlatanova, J., (1993). Preferential binding of histone H1 to four-way helical junction DNA.. Journal of Biological Chemistry. 268 (28), 20699-20700
Book chapters (4)
Choudhary, P. and Varga-Weisz, P., ATP-dependent Chromatin Remodelling. In: Subcellular Biochemistry. Springer Netherlands. 29- 44. 9781402054655
Varga Weisz, P. and El-Sahhar, S., (2022). The gut microbiome in health and disease: Inflammatory bowel diseases. In: Advances in Ecological Research. Elsevier. 289- 330. 9780323985932
Neves-Costa, A. and Varga-Weisz, P., (2006). The Roles of Chromatin Remodelling Factors in Replication. In: Results and Problems in Cell Differentiation. Springer Berlin Heidelberg. 91- 107. 9783540336853
Bozhenok, L., Poot, R., Collins, N. and Varga-Weisz, P., (2003). Functional Analysis of ISWI Complexes in Mammalian Cells. In: Chromatin and Chromatin Remodeling Enzymes, Part C. Elsevier. 376- 389. 9780121827816
Grants and funding
2021
Integrating cellular space and time: interplays between subcellular organisation and lifespan
Biotechnology and Biological Sciences Research Council
Acquisition of the Drosophila model system to understand mechanisms of innate immunity regulation by chromatin dynamics
National Centre for the Replacement Refinement & Reduction of Animals in Research
Genetic dissection of chromatin dynamics in bacterial pathogen defence using Drosophila
Genetics Society
Integrating cellular space and time: interplays between subcellular organisation and lifespan
Biotechnology and Biological Sciences Research Council
2018
Role of histone acylations in intestinal epithelium homeostasis
The Royal Society
Addressing the Inflammatory Bowel Disease Challenge in Vietnam by Bridging the Basic-Clinical Science Divide in Gastroenterology: A Vietnam-UK Collaborative Network
Academy of Medical Sciences
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