Marsden Funding “getting to the guts” of digestion research

Researchers from the Riddet Institute, based at the University of Auckland Bioengineering Institute (ABI) investigating the human digestive tract, have been awarded over $1 million by Te Pūtea Rangahau the Marsden Fund from the Royal Society Te Apārangi.

Dr Timothy Angeli, a former Riddet Institute PhD student and current researcher, has been awarded Marsden funding to research the finer points of the gut – more specifically, how the intestine communicates with the stomach.

“We bite, we chew, we swallow, we defecate,” says Dr Angeli. “These are the conscious actions that we perform during digestion, but there are also other underlying subconscious processes that move and digest food along our gastrointestinal tract to ultimately power our bodies and, if things go wrong, can seriously affect our health.”

Tim’s research will focus on a smooth muscle valve called the ‘pylorus’, a band of smooth muscle at the junction between the stomach and the small intestine. It plays a vital role in digestion, acting as a valve to control the flow of partially digested food from the stomach to the small intestine. The pylorus also selectively blocks or transmits different electrical signals between the stomach and intestine, but the mechanisms of this critical electrical communication remain a mystery.

Tim and his team including Riddet Institute Principal Investigator Professor Leo Cheng, will, with $300,000 of Fast Start Marsden funding, develop a high-resolution electrode device to map the electrical activity at this critical connection of the gut.

“Understanding the bioelectrical control between the stomach and intestine, across the pylorus, will help us better understand how digestion is coordinated, and may ultimately offer new treatment options to pylorus-related disorders.”

Associate Professor Peng Du, also a member of the Gastrointestinal Research Group at ABI and former Riddet Institute researcher, will be investigating the GI tract and has been awarded $900,000 in Marsden funding to do so.

Peng’s research is aimed at the development of a virtual model of the pylorus as well as two other major sphincters in the gut, the three main ‘muscular gates’ that regulate the flow of food within the gut. The digestive system is complicated, he says, and depends upon the actions (the closing and opening) of several sphincters in the gut, which are a combination of muscles and nerves and which are not well understood.

Peng explains that the controlling ‘gates’ are crucial. “If the pylorus doesn’t work properly, for instance, we can suffer from what is commonly known as ‘reflux’, a spectrum disorder that can affect people in different ways, from the minor to the severe. If it’s a more chronic problem, the acid that is being regurgitated into the oesophagus can burn the lining of the oesophagus, which can possibly lead to cancer.”

Peng and his team, including Professor Leo Cheng, will develop comprehensive models that combine X-ray microtomography (micro-CT) and high-resolution electromechanical mapping, to create virtual sphincters. This mathematical modelling can then be used to do predictive simulations of sphincter functions under different physiological conditions.

“Ideally we hope our research will lead to more understanding of how the gut operates. There’s a lot we can do modulating and controlling nerves, so if we have a better understanding of the activity of the nerves, we can use that to normalise gut actions when there are problems. An integrated modelling framework incorporating both structural and functional data will provide a new foundation that will guide new discoveries of future therapies, to allow for better neuromuscular control of the gut.”

“The gut is a complex and intricate organ, and normal functioning involves the coordination of contractions at different points in the gastrointestinal tract. This is something we can take for granted until things go wrong, and it certainly lets us know when it does.” he says.