Regulation of gene expression at the intersection of infection, inflammation and cancer
The extracellular matrix (ECM) is a highly active 3D network of secreted molecules that provides environmental signals which profoundly affect cell behaviour. Upon tissue damage and infection, ECM molecules that are absent or scarce in healthy tissues are transiently up-regulated at sites of injury where they support immune cell function in inflammation and tissue repair. However, deregulated and disorganised ECM is a hallmark of human diseases such as cancer, arthritis and neurodegenerative disorders.
We found rapid induction of a specific ECM glycoprotein during infection that enables an effective host response. Mechanistically, we discovered that it can sustain cytokine synthesis by regulating macrophage microRNA expression.
Defining how gene expression is regulated in the context of its cellular microenvironment can help us understand how the mechanisms that keep the immune response in check fail in disease and develop novel therapeutic strategies.
Projects are available to study how the cellular microenvironment modulates gene expression by regulating microRNA levels.
The successful applicant will use state of the art molecular, cellular and biochemical approaches. These will include CRISPR-CAS9 technology, RNA-Seq, real-time PCR, RNA interference, northern and western blot analysis and confocal microscopy. Cell lines as well as primary murine and human cell systems will be used.
The project will be carried out within the Gene Regulation & RNA Biology Group in the Division of Molecular & Cellular Sciences. The School of Pharmacy provides excellent cross-disciplinary support and training facilities for PG students.
Applications are welcome from motivated students with a good honours BSc or MSc degree in Science subjects. International applicants should meet the University requirements for English. Prospective candidates should visit our University pages for information regarding fees and funding at the University. Sponsored and self-funded students are welcome, and all applicants should contact the supervisors to discuss funding.
1) Piccinini A.M. and Midwood K.S. (2014). Illustrating the interplay between the extracellular matrix and microRNAs. Int J Exp Pathol 95 (3), 158-80.
2) Piccinini A.M. and Midwood K.S. (2012). Endogenous control of immunity against infection: tenascin-C regulates TLR4-mediated inflammation via microRNA-155. Cell Reports 2 (4), 914-26.
3) Goh F.G.*, Piccinini A.M.*, Krausgruber T., Udalova I.A., Midwood K.S. (2010). Transcriptional regulation of the endogenous danger signal tenascin-C: a novel autocrine loop in inflammation. J Immunol. 184 (5), 2655-62.
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