Prof Julia Cordero, University of Glasgow & Dr Johan Vande Voorde, University of Glasgow
Background
The adult intestine is a pivotal organ responsible for maintaining physiological, endocrine, immune, and metabolic equilibrium within an organism. Furthermore, the intestine actively participates in bidirectional communication with the central nervous system through the intricate gut-brain axis, which involves the central and enteric nervous systems, along with the endocrine and immune functions of the gut.
Therefore, intestinal disease is known to profoundly impact whole body physiology, including brain-controlled functions. Systemic effects of chronic intestinal inflammation and cancer include peripheric tissue wasting (also known as cachexia) and alterations in central nervous system-regulated behaviours such as sleep and feeding. Little is known about the mechanisms by which intestinal dysfunction impacts such complex host functions. Also, whether mechanisms driving cachexia and behavioural disfunction in colorectal cancer are connected, is unknown. The use of a genetically amenable in vivo model organism is invaluable for early discovery research in this fundamental area of biomedical science that mandates the study of the intestine its natural microenvironment and as part of a multi-organ system.
The fruit fly Drosophila melanogaster has pioneered behavioural and circadian biology research and provided invaluable insights into the study of cancer cachexia (1). Our preliminary results on Drosophila models of oncogene induced intestinal hyperplasia show that, disruption of gut health leads to profound effects in host metabolism, including cachexia like peripheric tissue wasting and disruption of normal feeding and sleeping patterns, which mimics the phenomenology reported in humans with colorectal cancer. Strikingly, we find a pivotal role of tumour derived lactate and immune-metabolic crosstalk between tumours and normal tissue in the intestine in cachexia.
Research Question
We will leverage the complementary expertise of the Cordero and Vande Voorde laboratories to study the mechanistic underpinnings of gut-regulated regulation of systemic function in the context of intestinal cancer, with a focus on the interplay between intestinal cancer- cachexia and sleep. Critically, this studentship will provide a framework for cross validating findings in different model organisms (i.e. Drosophila melanogaster and Mus musculus).
- How does metabolic and immune reprograming of intestinal tumours impact organismal physiology and systemic tissue wasting? Initially, this will focus on strong preliminary data from the Cordero Laboratory identifying tumour-derived lactate as a critical signalling metabolite in cachexia.
- How do intestinal tumours affect essential life behaviours such as sleeping and feeding? This will capitalize on the expertise of the Cordero lab using complex models in Drosophila for independent genetic manipulation of the intestine and peripheric tissues (muscle, adipose tissue and distinct cell populations in the brain), and dovetails with ongoing collaborative work between the Vande Voorde/Sansom labs focusing on characterization of mouse models of CRC cachexia.
Skills/Techniques that will be gained
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Drosophila melanogaster and mouse genetics: Advance genetics including a diverse range of genetic toolkits in both model organisms.
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Intestinal biology: tissue dissection, staining and imaging.
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Cancer biology: intestinal cancer, stem cells and cancer.
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Metabolism: including the assessment of metabolic function in vivo, and use of LC-MS based tissue metabolomics (including data analysis and interpretation)
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Transcriptomics: Including the use of RNA sequencing (bulk and single nuclei RNA sequencing).
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Behavioural biology: performing and analysing feeding and sleeping behaviours in Drosophila and learning of the basic neurobiology behind such behaviours.
To place an application, please visit this site at the CRUK Scotland Institute.
When submitting your application please make sure that you have also completed your application to the Windsor Fellowship and please upload the completed recruitment form.
Duration: 4 years, starting October 2026
Closing Date: 24th November 2025
Interview for this position will take place in January 2026
Lab Websites
Prof Julia Cordero - Local and Systemic Functions of the Intestine in Health and Disease
Dr Johan Vande Voorde - Metabolic Crosstalk in Cancer
Relevant Publications
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Medina A, Bellec K, Polcowñuk S, Cordero JB. Investigating local and systemic intestinal signalling in health and disease with Drosophila. Dis Model Mech. 2022; 15:dmm049332
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Medina AB, Perochon J, Tian Y, Johnson CT, Holcombe J, Ramesh P, Polcowñuk S, Yu Y, Cordero JB. Neuroendocrine control of intestinal regeneration through the vascular niche in Drosophila. Dev Cell. 2025.
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Phillips JA, Perochon J, Johnson CT, Walker M, Nixon C, Hughes M, Barros-Carvalho A, Yu Y, Mitchell L, Blyth K, Vassalli M, Cordero JB. Intestinal Tissue Mechanics Regulate Angiogenesis and Stem Cell Proliferation via Vascular Piezo. bioRxiv. 2025:2025.2004.2016.649133.
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Vande Voorde J, Steven RT, Najumudeen AK, Ford CA, Dexter A, Gonzalez-Fernandez A, Nikula CJ, Xiang Y, Ford L, Maneta Stavrakaki S, Gilroy K, Zeiger LB, Pennel K, Hatthakarnkul P, Elia EA, Nasif A, Murta T, Manoli E, Mason S, Gillespie M, Lannagan TRM, Vlahov N, Ridgway RA, Nixon C, Raven A, Mills M, Athineos D, Kanellos G, Nourse C, Gay DM, Hughes M, Burton A, Yan B, Sellers K, Wu V, De Ridder K, Shokry E, Huerta Uribe A, Clark W, Clark G, Kirschner K, Thienpont B, Li VSW, Maddocks ODK, Barry ST, Goodwin RJA, Kinross J, Edwards J, Yuneva MO, Sumpton D, Takats Z, Campbell AD, Bunch J, Sansom OJ. Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target. Nature Metabolism. 5(8):1303-1318