Dr Elizabeth Ballou is 2022 Lister Fellow and a medical mycologist based at the University of Exeter. She is a Wellcome Trust Henry Dale Fellow and Principal Investigator at the MRC Centre for Medical Mycology.
We spoke with Liz about her journey into science, observing shape-shifting fungal pathogens, and her recent Wellcome Trust grant for bioimaging.
Q: Tell us a little about your background. What came first, medicine or mycology?
A: I came to science from the medical side first. Throughout my life my father was heavily involved in developing the RTS,S malaria vaccine, which found success around the time I started college. So I was coming into science on this inspirational wave of possibility. I had a strong desire to use my research to make the world a better place, and that’s always been a guiding principle for me. Science is an incredible mechanism for improving human health and wellbeing and learning about the world.
I studied chemistry in college. I was a synthetic protein chemist at a time when we were starting to understand the importance of protein structures to protein function. Genomes were being sequenced and it was clear that a whole area of new information could be learned by reading genetic code. I realised that in order to access that world I needed a degree in molecular biology, so I enrolled in the Molecular Biology of Infectious Disease programme at the London School of Hygiene and Tropical Medicine. There I found a global community of brilliant researchers who are all trying to use science to solve problems for their communities.
My introduction to medical mycology came later, after a year spent participating in vaccine research in the USA, where I’m from. I applied to Duke University with the intention of studying molecular biology and biochemistry. Duke is a world centre for medical mycology, although I didn’t know that when I went there. I very quickly stumbled into a research clinician called Andy Alspaugh and became his first graduate student, studying Cryptococcus neoformans, a fungal pathogen which affects mostly people in resource-limited settings, especially in Africa. He is a very supportive mentor.
I had a strong desire to use my research to make the world a better place, and that’s always been a guiding principle for me.
Q: What kind of unique challenges do fungal pathogens present?
A: One of the things I learned from studying Cryptococcus is that how we see these organisms in the lab is not the way they exist in the body. They have a much more complex way of growing and causing disease in humans. That insight is the basis of one of my lab’s streams of work.
Cryptococcus can change from a small yeast form, measuring about 5 microns, to really gigantic ‘Titan cells’ which are 100 microns or more. These evade the immune response and are a major source of drug resistance, but they are difficult to grow outside of the body. Serendipitously, a student in my lab hit on the correct parameters to grow Titan cells, which had been a big challenge for the research community.
Another challenge is timely and accurate diagnosis. This issue is central to another area of my lab’s work, mucormycosis, which is the project funded by the Lister Prize. Mucormycosis is a really damaging infection caused by a group of fungal pathogens called Mucorales that enter the body through the airways. It’s an extremely aggressive fungus and mucormycosis can be very disfiguring for survivors, though only 50%-60% of people do survive it. It had a big impact during COVID-19, when people who were taking steroid medication became more susceptible to the fungus.
In just two weeks a person can go from being completely well to having this terrible, destructive infection – so rapid, early diagnosis is crucial in order to catch it as soon as possible. However, it’s difficult to diagnose because it’s rare, and most people aren’t thinking of it when a patient presents with symptoms.
Mucorales aren’t very similar to other well-studied fungi, so there aren’t many tools we can use to test for it. Diagnosis relies mostly on histological diagnosis – looking at tissue sections – which demands a lot of expertise.
Q. What methods do you use to study fungi like Mucorales and Cryptococcus?
A: Microscopy is really important in my lab. I always tell my students ‘Look at your cells. What are they doing?’ It’s really easy to be drawn into molecular and higher-level phenotypic tests and overlook what we can learn from observing the organisms.
We partner with a company called ISCA Diagnostics which has been culturing all kinds of fungal pathogens and collecting antigens, then developing antibodies. We wanted to understand more about what the antibodies for mucormycosis are binding to.
Alyssa Hudson is a clinician and graduate student who did a master’s project in my lab. She was funded by Noah’s Pink Balloon, a charity founded by a UK family who lost a child to mucormycosis. Using microscopy, Alyssa discovered not only that the antibodies can detect the antigen on the surface of the fungus, but that they are expressed specifically during invasive infection. That means we have a really important tool for accurately identifying damaging infections, rather than just people who have breathed in spores from the environment that aren’t invading their tissues.
Alyssa’s data is very eye-catching – so much so that she’s been able to do public engagement through talks and presentations because her images are really beautiful. She’s also been invited to give talks about the work at a number of international conferences. This kind of impact is crucial to raising awareness of mucormycosis among clinicians, which will help overcome treatment challenges. We’re grateful to both the Lister Institute and Noah’s Pink Balloon for their support in enabling this kind of work.
Microscopy is really important in my lab. I always tell my students ‘Look at your cells. What are they doing?’
Q: You recently received a Wellcome Trust grant for bioimaging. Can you tell us more about that?
A: The Wellcome Trust has made a large investment in advancing microscopy and making it as widely accessible as possible. The WHO has published a list of 20 priority fungal pathogens, many of which are understudied because of a lack of tools and infrastructure. The project will develop a bioimaging toolkit that can be used for multiple types of priority fungi, and also imaging technologies and data analysis tools.
We put together a team that includes my group at the University of Exeter, working on cryptococcus and mucormycosis bioimaging, a group at the University of Edinburgh who are experts in microfluidics and high data throughput analysis, and a group at the University of Cape Town, South Africa that studies an emerging fungal pathogen called Emergomycosis africanus.
One aspect I’m particularly proud of is that we’re running a course to provide these tools and trainings to medical mycologists at the University of Cape Town in the summer, along with the African Microscopy Initiative, funded by CZI, and UCT’s Institute of Infectious Disease and Molecular Medicine. Together, we are widening access to this technology for scientists who can use it to deliver on their own research objectives.
Q: How has the Lister Prize impacted your research so far?
A: I’m really thankful to the Lister Institute for enabling my research on mucormycosis. I had been working on it in an unfunded way for many years alongside my other interests. It can be challenging to get funding for work that isn’t already being addressed, so when the Lister opportunity arose, it was transformative. It has meant we can make progress in an area that affects a lot of people globally, and we have challenged assumptions about how this organism causes disease. The Lister catalysed the growth of a team of clinical and basic researchers in my lab, including Alyssa and also clinician scientist Dora Corzo-Leon, an expert in clinical presentations of mucormycosis. In addition to the imaging work, they’re developing new animal models to study infection progression and diagnostic challenges. So the money has been important not only for me, but for raising the profile of mucormycosis globally and strengthening the research community.
Learn more about the work of the Ballou Lab at the University of Exeter
