Patrick Varga-Weisz

As of April 2018, Patrick has taken up a Lectureship in the School of Biological Sciences at the University of Essex. Visit his page there for full details of his current research.

Research Summary

Chromatin is a highly dynamic structure to accommodate its many tasks in regulating, organizing, safeguarding and packaging the genetic material. We are interested in understanding the mechanisms behind this sophisticated cellular machinery.

Key components that impart this dynamic state are special enzymes, so called chromatin remodelling factors, many of which target the nucleosome, the basic building block of chromatin.

The enzymology of chromatin remodelling is a largely new territory with opportunities for many exciting discoveries. One particular class of chromatin remodelling factors uses the energy gained by ATP hydrolysis to remodel nucleosomes: The nucleosome may be shifted, altered or blasted away, but some of these factors, such as Imitation Switch (ISWI), are also involved in nucleosome assembly.

The Varga-Weisz laboratory studies such ATP-dependent nucleosome remodelling factors, their role in the cell (in chromatin replication) and their mechanisms of action.

Latest Publications

Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium.
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, Varga-Weisz P

How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue.

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Genome biology, 21, 1, 11 Mar 2020

PMID: 32160911

Chromatin dynamics and histone modifications in intestinal microbiota-host crosstalk.
Fellows R, Varga-Weisz P

The microbiota in the human gut are an important component of normal physiology that has co-evolved from the earliest multicellular organisms. Therefore, it is unsurprising that there is intimate crosstalk between the microbial world in the gut and the host. Genome regulation through microbiota-host interactions not only affects the host's immunity, but also metabolic health and resilience against cancer. Chromatin dynamics of the host epithelium involving histone modifications and other facets of the epigenetic machinery play an important role in this process.

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Molecular metabolism, 1, 1, 27 Dec 2019

DOI: 10.1016/j.molmet.2019.12.005

PMID: 31992511

Transcriptome analysis identifies a robust gene expression program in the mouse intestinal epithelium on aging.
Kazakevych J, Stoyanova E, Liebert A, Varga-Weisz P

The intestinal epithelium undergoes constant regeneration driven by intestinal stem cells. How old age affects the transcriptome in this highly dynamic tissue is an important, but poorly explored question. Using transcriptomics on sorted intestinal stem cells and adult enterocytes, we identified candidate genes, which change expression on aging. Further validation of these on intestinal epithelium of multiple middle-aged versus old-aged mice highlighted the consistent up-regulation of the expression of the gene encoding chemokine receptor Ccr2, a mediator of inflammation and several disease processes. We observed also increased expression of Strc, coding for stereocilin, and dramatically decreased expression of Rps4l, coding for a ribosome subunit. Ccr2 and Rps4l are located close to the telomeric regions of chromosome 9 and 6, respectively. As only few genes were differentially expressed and we did not observe significant protein level changes of identified ageing markers, our analysis highlights the overall robustness of murine intestinal epithelium gene expression to old age.

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Scientific reports, 9, 2045-2322, 2019

PMID: 31320724