“Although women make up half of the global population, women’s health has been historically understudied. Up to 75% of women experience a fungal vaginal infection in their lifetime which is a huge global disease burden,” says Quadram Institute researcher Dr Emily Jones.

Emily is leading a Clinical Seedcorn project together with Dr Paul Simpson Consultant Gynaecologist at the Norfolk and Norwich University Hospital to develop a new organ-on-chip system. The system will be used to study the principle fungus responsible for causing vaginal candidiasis, also known as thrush infections.

The Clinical Seedcorn fund is designed to help clinicians develop research ideas with scientists at the Quadram Institute and is jointly funded by the Quadram Institute and the Norfolk & Norwich Hospitals Charity.

The clinical challenge of Candida albicans

The main fungus responsible for thrush is called Candida albicans.

“The likelihood of having a Candida infection at some point in your lifetime is quite high. For most women it’s a one-time event treated with an antimicrobial medicine that tends to sort out the problem,” says Paul.

Symptoms can range from mild to debilitating and recurrent as Paul highlights, “Unfortunately, as with other infections in the body, the infection can become more longstanding and more difficult to treat. In these cases, we use medicines over a more prolonged time period, which sometimes requires the use of several antifungal medicines.”

Paul continues, “The problem with any bacteria or fungus, exposed to a medicine for a long time, is that the microbe can develop resistance. Resistance among strains of Candida is becoming increasingly a problem clinically, and it becomes difficult to treat that infection, particularly in anyone that has a supressed immune system.”

How gut-on chip systems can help study candidiasis

“The idea for the project came about when we realised there aren’t many models to study this area of women’s health,” says Emily.

Emily is an expert in developing organ-on-chip systems, which allow researchers to study how human tissues behave in the lab. She has previously developed systems to study the gut, brain, and lungs.

Emily explains more, “We’re using a miniature organ on chip system called a microphysiological system. In this system we grow human epithelial cells collected from patient vaginal swabs. We can then add Candida albicans and study how the fungus interacts with the vaginal cells.”

“At the Quadram Institute we have a fantastic Advanced Microscopy facility. As part of this Clinical Seedcorn project we’ll work closely with the facility to look at vaginal and fungal cells in the system under the microscope. We’ll use techniques such as high-resolution microscopy to learn more about how the fungi invade the cells and how they can disseminate away from the vaginal cells.”

Learning about the vaginal microbiome with a focus on fungi

Along with working with the Advanced Microscopy Facility at the Quadram Institute, Emily will also be working with fungal researcher Dr Steve James.

Steve explains more, “My role is to look at the fungal component of the human microbiome. My interest is yeast and other fungi in the gut and elsewhere.”

“I’ve been working with Candida albicans since I first joined Professor Simon Carding’s Group at the Quadram Institute eight years ago. Primarily I’ve been looking at Candida species in the gut but there’s a huge gap in women’s health. There’s lots of research about the gut microbiome but far less about the vaginal microbiome.”

“I’m especially interested in investigating how Candida albicans can switch from being a commensal fungus, causing no problems at all, to being an opportunistic pathogen, causing disease. In the project we’ll look at different tissue samples collected from women who either have vaginal candidiasis or are totally asymptomatic.”

The  Clinical Seedcorn project builds on work from a previous Proof of Concept award to Emily and Steve, where they looked at the interaction between the fungus and vaginal cells under the microscope.

Steve explains more, “We’ve previously looked at infecting vaginal and epithelial cells but not in the organ-on-chip system. We saw how different clinical isolates can cause variable degrees of cell damages. For instance, a vaginal isolate from a patient with candidiasis damaged the epithelial cells far more than an isolate from the someone without symptoms.”

“The interesting thing about Candida albicans is that it’s a dimorphic fungus. This means it can switch between being in an oval yeast form to a hyphal form in long filaments. When the fungus transitions to a hyphal form, it switches to becoming invasive and produces a cytolytic toxin called candidalysin. This toxin damages the cells and allows the fungus to invade the human cells,” says Steve.

Along with support from the Advanced Microscopy Facility at the Quadram Institute, the team will be making use of other expertise within the Institute. Steve highlights, “Using our excellent Sequencing facility run by Dave Baker we’ll study the genetics of the fungus to see whether there is anything different between the vaginal isolates causing symptoms compared to those that don’t cause any symptoms.”

Power of collaboration between bioscience and medicine

This Clinical Seedcorn project highlights the potential of bringing together scientists and clinicians to tackle health challenges.

“This is the first project I’ve worked with clinicians at the Norfolk and Norwich University Hospital. We’re really excited to start this project,” says Emily.

She continues, “The results from this project will help improve methods for preclinical evaluation of fungal infections in women’s health. This could lead to improved clinical diagnostic testing and new antifungal treatments.”

Steve adds, “We believe that if you can keep Candida albicans locked in the its commensal-associated yeast form, then it’s much less likely to cause infection.”

Paul has a long interest in research as a clinician, “I find research interesting and engaging. Going back a bit, I did a science degree first before I went to medical school. I spent the whole of my gap year in a microbiology lab. I’m quite familiar with working with scientists and understanding how biological science and medicine link.”

He continues, “I took time out of my medical degree training programme and spent three years doing a research degree at the University of East Anglia looking at a new treatment for endometriosis which is the type of care I now undertake. In my current role I do a range of research studies.”

Paul was part of a team at the hospital to be part of a world-first endometriosis drug trial.

He reflects, “Being part of research is an opportunity to contribute to understanding the biology not just for our population in Norfolk, but across the UK and even wider outside the UK.”

“The Clinical Seedcorn project is a relatively early-stage project. It’s about developing this organ-on-chip model that will then hopefully build to bigger studies, with more patients involved and where you might start to use that model to learn more about how you develop a clinical medicine.”

He concludes, “In this particular context, neither us clinicians or the scientists could do what we want to do alone so you have to collaborate between different people and different organisations to make it possible.”

Banner image credit: Dr Emily Jones and the Advanced Microscopy Facility