Completed Cells, Biochemistry & Physiology Diabetes, Hormones & Metabolism

Proton coupled transporters in health and disease.

Funder Wellcome Charity-funded
Recipient organisation University of Oxford
Funding £2.1M
Period Aug 2019 — Aug 2024

In plain English

AI plain-English summary

Every time you swallow a pill, a tiny protein gatekeeper in your gut lining decides whether that drug gets into your bloodstream or gets flushed out. These gatekeepers are proton-coupled transporters, and scientists still do not know exactly how they work. This research aims to close that gap. The proteins in question—belonging to the SLC15, SLC36, and SLC46 families—are responsible for moving nutrients like peptides, amino acids, and folate into cells, and they also handle many common oral drugs. Despite their central role in metabolism and drug absorption, their three-dimensional structures and the precise mechanisms by they recognise and transport molecules remain largely unknown. The researcher will combine structural biology, biochemistry, and biophysics to determine how these transporters recognise their cargo, how they move it across membranes, and how they are regulated in different cellular environments. A key output will be accurate pharmacophore models—essentially molecular blueprints—that explain how drug molecules are recognised and translocated. If successful, this fundamental science could enable pharmaceutical companies to design drugs that hitch a ride on these transporters more efficiently, improving drug uptake and retention in the body. That could mean lower doses, fewer side effects, and better treatments for conditions ranging from infections to metabolic disorders.

View original technical description
Proton coupled transporters play important roles in human health and disease, being responsible for the uptake and distribution of nutrients into the body and between organs, regulating metabolism and impacting the pharmacokinetic profiles of orally administered drug molecules. Remarkably, given their importance in cell biochemistry, little is understood regarding their structure, mechanism of action or regulation. This proposal seeks to close this gap in our knowledge. Using a combination of structural, biochemical and biophysical approaches I will determine the molecular basis for ligand recognition, transport and regulation within the peptide (SLC15), amino acid (SLC36) and folate (SLC46) transporter families. This research will establish the mechanism by which these proteins transport nutrients and drug molecules into the cell and across organellular membranes, facilitating a more rational strategy to improve drug uptake and retention in the human body. My key goals are: - Determine the molecular basis for proton coupled nutrient and drug transport into eukaryotic cells. - Develop accurate pharmacophore models that explain how drug molecules are recognised and translocated across membranes. - Reveal the mechanisms that regulate these systems in different membrane environments and organelles. - Engage with the pharmaceutical industry to advance drug design and delivery within the human body.

View the original record at the funder ↗

Researchers

Simon Newstead (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Drug transport through human peptide transporters
Structure-function studies on mammalian peptide transporters.
Resolving mechanistic details of peptide transport across membranes using crystallographic and non-crystallographic structural biology approaches
Structure/function analysis of the ubiquitous SLC26A/SulP transporter/channel family
The roles of transporters in the human metabolic network

Original classification

Investigator Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.