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Dr Golnar Kolahgar

Extrinsic regulation of intestinal proliferation and gut maintenance in Drosophila
Dr Golnar Kolahgar

Sir Henry Dale Fellow


Research Interests

The intestinal epithelium constantly regenerates from stem cells, which adjust their behaviour to the changing physiological conditions the gut is exposed to. For example, stem cell proliferation rates can transiently increase to speed up regeneration after tissue loss or in response to the diet, before reverting to steady-state levels once correct tissue size is reached. This plasticity is essential for intestinal function, as lack of regeneration causes tissue atrophy whereas unrestricted stem cell proliferation promotes cancer.

 

Our aim is to identify the secreted and physical factors regulating gut plasticity. We focus on discovering extracellular molecules that instruct cells to proliferate in the gut and on investigating the crosstalk between the visceral mesoderm and the intestinal epithelium. We work with the intestine of the fruit fly Drosophila due to the ease with which it can be genetically manipulated and imaged with sophisticated microscopy, its rapid lifecycle and because it is cost-effective. Importantly, this organism shares more than 70% of its DNA with human disease genes, meaning that our basic research has the potential to uncover new insights into intestinal maintenance and degenerative diseases.

Funding: Wellcome Trust / Royal Society

Collaborators

Prof Nick Brown (PDN)

Key Publications

Kucinski I*, Dinan M*, Kolahgar G, Piddini E (2017), Chronic activation of JNK, JAK/STAT and oxidative stress signalling causes the loser cell status; (* equal contribution); in press, Nat. Commun.

Suijkerbuijk SJE, Kolahgar G, Kucinski I, Piddini E. (2016), Cell competition drives the growth of intestinal adenomas in Drosophila. Curr Biol. 2016 Feb 22;26(4):428-38

Kolahgar G, Suijkerbuijk SJE, Kucinski I, Poirier E, Mansour S, Simons BD, Piddini E. (2015) Cell competition modifies adult stem cell and tissue population dynamics in a JAK-STAT dependent manner. Dev Cell. 2015 Aug 10, 34(3):297-309

Wagstaff L*, Kolahgar G*, Piddini E, (2013), Competitive cell interactions in cancer: a cellular tug of war. Trends Cell Biol. 2013 Apr;23(4):160-7 (* equal contribution)

Vincent JP, Kolahgar G, Gagliardi M, Piddini E, (2011), Steep differences in Wingless signaling trigger Myc-independent competitive cell interactions. Dev Cell. 2011 Aug 16; 21(2):366-74

Kolahgar G*, Bardet PL*, Langton P, Alexandre C, Vincent JP, (2011), Apical deficiency triggers JNK-dependant apoptosis in the embryonic epidermis of Drosophila. Development. 2011 Jul 138(14):3021-31 (* equal contribution)

Bardet PL, Kolahgar G, Mynett A, Miguel-Aliaga I, Briscoe J, Meier P, Vincent JP, (2008), A fluorescent reporter of caspase activity for live imaging. PNAS. 2008 Sep 16;105(37):13901-5

Antoine K, Ferbus D, Kolahgar G, Prosperi MT, Goubin G, (2005), Zinc finger protein overexpressed in colon carcinoma interacts with the telomeric protein hRap1. J Cell Biochem. 2005 Jul 1;95(4):763-8

Postdoc position available here

Above: Cross section (top panel) and superficial section (bottom panel) of a portion of Drosophila midgut. The visceral muscles and epithelial cell walls are labelled with phalloidin (white) and nuclei markers (yellow and purple)

Above: Progenitor cells (green) in the Drosophila posterior midgut. Nuclei are marked with DAPI (blue)

Above: Tumour cells (green) observed from the inside of an adult Drosophila gut (red)