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Novel drugs and receptors for targeting neural control of digestive function

Disorders of colorectal function, particularly constipation, have no adequate treatment. We have identified several targets that are amenable to drug development that we are investigating in animal models.

Aims

You will work with a team of researchers to investigate the effectiveness and mechanisms of action of novel pharmacological tools.

We have made a number of discoveries of new compounds that can modify digestive function, and are conducting animal proof of principle experiments that we hope will lead to clinical trials.

This project will provide you with the opportunity to conduct in vivo experiments and to learn much about whole animal physiology. One of the major problems of digestive function is failure of propulsive activity. This arises from a variety of neuro‐muscular dysfunctions. The most common result is constipation that afflicts more than 20% of the population, many older Australians and most of those with spinal cord injury. We have discovered several new classes of drugs that can potentially be used to treat these conditions and this project will further investigate the mechanisms of action and therapeutic potential of novel compounds.

References:

Pustovit, RV, Callaghan, B, Ringuet, MT, Kerr, NF, Hunne, B, Smyth, IM, Pietra, C, Furness, JB: Evidence that central pathways that mediate defecation utilise ghrelin receptors but do not require endogenous ghrelin. Physiol Reports, 5, e13385 (2017)

Pustovit, RV, Itomi, Y, Ringuet, M, Diwakarla, S, Chai, X-y, McQuade, RM, Tsukimi, Y, Furness, JB: Muscarinic receptor 1 allosteric modulators stimulate colorectal emptying in dog, mouse and rat and resolve constipation. Neurogastro Motil 13 e13692 (2019) DOI: 10.1111/nmo.13692

Diwakarla S, Bathgate, RAB, Zhang, X, Hossain, MA and Furness, JB: Colokinetic effect of an insulin-like peptide 5 related agonist of the RXFP4 receptor. Neurogastro Motil 32, e13796 (2020)

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