Prof John O'Sullivan and the Cardiometabolic Disease Group at the Heart Research Institute (HRI) have been collaborating with Prof Christopher Loughrey at the University of Glasgow, Scotland, UK on a research project investigating new therapeutic strategies for stiff heart failure. This research is supported by a grant funded by HRI UK donors to advance research into cardiovascular disease.
Dr Yen Chin Koay, a postdoctoral scientist with the Cardiometabolic Disease Group in Sydney, Australia spent six months working in Prof Loughrey’s lab in Glasgow. She provides an update on how this important meeting of the minds has helped bring a treatment for stiff heart failure one step closer.
What is stiff heart failure (HFpEF)?
Stiff heart failure, otherwise known as heart failure with preserved ejection fraction (HFpEF), is a type of heart failure where the heart can contract normally but cannot relax properly, due to stiffening of the left ventricle.
Heart failure affects over 64 million people worldwide; nearly half of these patients have “stiff” heart failure. In the UK, over 400,000 people have stiff heart failure. In Australia, an estimated 250,000 people have stiff heart failure and over 60,000 Australians are newly diagnosed with stiff heart failure every year.
Despite the prevalence of stiff heart failure, there is still no effective therapy to treat it.
What kind of research into HFpEF did you conduct in Glasgow?
Prof Loughrey’s laboratory specialises in fundamental research of the mechanisms underlying the two main types of heart failure, HFpEF and myocardial infarction (MI – otherwise known as heart attack), with a primary goal of comprehending the fundamental mechanisms that cause these conditions.
During my time in Prof Loughrey’s lab, I acquired the skills to perform primary adult cardiomyocyte cell culture, as well as how to isolate and grow cardiomyocytes (heart muscle cells) from cardiac tissues in lab models of heart failure.
I also conducted mitochondrial assays to study the changes in mitochondrial function that occur in both HFpEF and MI.
How has this helped in the search for a treatment for HFpEF?
With the help of these techniques, I have been able to study the function and behaviour of cardiomyocytes derived from HFpEF hearts in a controlled environment, allowing me to gain a better understanding of the underlying mechanism of HFpEF. Mastering these techniques has also allowed me to test new drugs aimed at targeting these changes in cardiomyocytes.
The ability to conduct primary cardiomyocyte culture in our laboratory has immensely contributed to our research. We are now able to use a combination of techniques, including mass spectrometry to track ketogenesis and gain insights into the role of ketogenic enzymes in the regulation of mitochondrial function, an essential aspect of our research. This helps grow our knowledge of HFpEF and will assist in uncovering new therapeutic strategies to help people with HFpEF.
How did this collaborative project help advance your research skills and career?
It has been an eye-opening experience for me to learn and be exposed to different methods and new techniques that were not available in our research group. In turn, it was satisfying to help set up new processes in Prof Loughrey’s lab, such as a specific method for MI heart tissues that the lab is now using to assess mitochondrial function.
This sabbatical has also provided an opportunity to identify new questions or directions for my research that have not been considered before, as well as to establish new collaborations and research and grant opportunities. Indeed, we were recently awarded Prime Pump Funding (a joint funding between the University of Glasgow and the University of Sydney), which afforded me the opportunity to travel to the University of Glasgow to gain knowledge on genetic modifications in primary cardiomyocytes with Prof Stuart Nicklin and Prof Loughrey.
Due to the geographical proximity, I was able to attend the XXIV World Congress International Society for Heart Research (ISHR) in Berlin, Germany, where I was awarded the International Poster Prize. I also attended the international Oroboros course on high-resolution respirometry in Innsbruck, Austria, in which I was exposed to new techniques in conducting mitochondrial research. This has helped me stay up-to-date with the latest research in the mitochondria field, which could potentially give rise to new directions in our search for a therapy for HFpEF.
How do UK labs and Australian labs differ in operation?
The regulatory environments in the UK and Australia differ regarding research ethics, which can impact the conduct of research in the two countries. The research focus also differs, as UK labs appear to have a strong emphasis on basic science, while Australian labs have a strong emphasis on medical science and translational research.
Although there may be some differences in the way research labs in the two countries operate, the overall goal is the same: to conduct high-quality, cutting-edge research that advances scientific knowledge.
What advice would you give to a researcher who is looking to work in a lab internationally?
It’s important to research the country as well as the specific lab you are interested in working with. Be open-minded and ready to learn and adapt to different working styles, communication and cultural differences. It can be a great opportunity to learn new techniques, gain new perspectives on research and connect with people in different fields.