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Investigating the role of intestinal nutrient transporters in physiology and disease

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  • Full or part time
    Dr S Hirabayashi
    Dr I Miguel-Aliaga
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Membrane nutrient transporters are at the forefront of nutrient sensing and uptake that supports intestinal organ physiology and plasticity. Intestinal epithelial cells respond and adapt to environmental nutritional challenges as well as to internal challenges such as reproduction (1,2). Cancer cells require a constant supply of extracellular nutrients to support their proliferation. In addition, changes in nutrient availability in the presence of a perturbed systemic metabolic network associated with obesity impacts cancer development and progression (3, 4). However, the contribution of intestinal nutrient transporters to gastrointestinal tumours and metabolic disorders remains largely unexplored.
We use the fruit fly Drosophila melanogaster as a whole-animal model system to study the physiological plasticity of the intestinal epithelium in response to nutritional challenges. We also use Drosophila models of colorectal cancer to study the interplay between diet-induced obesity and tumour progression. The project (i) will identify intestinal nutrient transporters that sustain normal physiology and/or lead to gut tumour pathology, and (ii) will explore how their effects are modulated by diet and internal state. The fly model will allow us to manipulate identified transporter expression with temporal and spatial control, to probe the links between nutrition and disease in the context of intestinal physiology and pathophysiology. To this end, the project will make use a diverse range of state-of-the-art approaches – from imaging of single gut cells to whole organ transcriptomics/metabolomics to whole-body behavioural and physiological assays.

Lab homepage:
https://lms.mrc.ac.uk/research-group/metabolism-cell-growth/
https://lms.mrc.ac.uk/research-group/gut-signalling-and-metabolism/

Funding Notes

This project is competition funded for students worldwide.

If successful the student would receive full tuition fee payment for 3.5 years as well as a tax free stipend amounting to £21,000pa paid in monthly instalments for the duration of their studentship.

Whilst Overseas Students are eligible, funding is more limited so only exceptional OS students will be considered.

References

Hudry B, Khadayate S, Miguel-Aliaga I. (2016). The sexual identity of adult intestinal stem cells controls organ size and plasticity. Nature. 530, 344.

Reiff T, Jacobson J, Cognigni P, Antonello Z, Ballesta E, Tan KJ, Yew JY, Dominguez M, Miguel-Aliaga I. (2015) Endocrine remodelling of the adult intestine sustains reproduction in Drosophila. Elife. 4, e06930.

Hirabayashi S and Cagan RL. (2015). Salt-inducible kinases mediate nutrient-sensing to link dietary sugar and tumorigenesis in Drosophila. Elife. 4, e08501.

Hirabayashi S, Baranski TJ, Cagan RL. (2013). Transformed Drosophila cells evade diet-mediated insulin resistance through wingless signaling. Cell. 154, 664-675.



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