15 November 2021
Professor Mike Berridge’s decades-long scientific career spans the globe and several fields from plant biology to cancer metabolism where his discoveries have challenged some paradigms of molecular biology that he grew up with. His significant and continued contribution to research has now been recognised with the prestigious Shorland Medal, awarded by the New Zealand Association of Scientists.
Science is unpredictable and continually encroaching on new frontiers. Professor Mike Berridge’s career, which began more than 50 years ago, has perpetually positioned him at the frontier of his field. As one of the founding scientists at the Malaghan Institute of Medical Research, Prof Berridge has helped propel scientific research in New Zealand to the world stage.
“It's in my nature to ask questions”, says Prof Berridge. “One thing I've learned as a scientist is that you have to be comfortable with the unknown and asking questions is the way to focus your research and find some answers.”
In 2015, his research experience and ability to ask the right questions came together in the form of an unexpected discovery that shook the foundations of the field of cell biology. Prof Berridge discovered that mitochondria, the structures in our cells that provide our body with most of its energy, are able to jump from a healthy cell to a cancer cell which lacks its own functioning mitochondria.
To truly appreciate why this discovery was so surprising, we must look at what we know about the DNA in our cells. Much of our DNA is constrained at the centre of our cells in a fiercely protected structure called the nucleus. However, there is a tiny but essential part of our DNA, which is often overlooked, within these tiny mitochondria that move around in our cells.
“At the time, it was widely accepted that the genes in our DNA that encode proteins are constrained within cells and partition between cells when they divide,” says Prof Berridge.
However, Prof Berridge’s finding suggests that in times of cellular stress, the mitochondria, along with the DNA inside them, can move from one cell to another.
“Since cancer cells are in a continuous state of stress, this may be a mechanism used by tumours to overcome this stress and continue to grow and wreak havoc on the body.”
This discovery has opened a whole new avenue of research that Prof Berridge and his team continue to investigate at the Malaghan Institute in collaboration with research teams at Griffith University and in Prague.
“It's in my nature to ask questions”, says Prof Berridge. “One thing I've learned as a scientist is that you have to be comfortable with the unknown and asking questions is the way to focus your research and find some answers.”
Having spent his early years north of Auckland and loaded with an arsenal of questions, studying science seemed like the natural course of action to satiate his curiosity. After completing a PhD in plant cell growth at the University of Auckland in 1971, he headed to the United States where he undertook a post-doctoral position at Purdue University. Here, he was able to apply his knowledge of cell development in plants to characterise how genes are expressed during animal development. At this time, the structure of DNA had only been known for 20 years. Knowledge of how the body can extract information from this unassuming molecule and synthesise the complex array of structures that make up every component of our body was still to be established. He published notable research articles that helped lay the foundations of molecular cell biology, a field which has emerged and grown exponentially over the last few decades. Despite this rapid advancement, his early papers still hold relevance.
“It’s quite surreal to see that the papers we published fifty years ago are still occasionally cited,” says Prof Berridge.
Having worked in the United States and then the United Kingdom, in 1976 Prof Berridge was given the opportunity to start his own research group back home in New Zealand at the newly established Wellington Cancer and Medical Research Institute, later renamed the Malaghan Institute of Medical Research. Over the next few years, he kick-started his Cancer Cell and Molecular Biology research team by investigating stem cell differentiation in blood cells.
Mike Berridge with the Institute's first BD FACS2 fluorescence activated cell sorter (1986)
“From here on, I had the flexibility to follow my desired line of questioning. I was able to direct my research and collaborate with other research groups to build knowledge thorough experimentation,” says Prof Berridge.
In fact, one of these collaborations came from an unexpected encounter with a researcher, Dr Fu-Kuen Lin, who worked in an adjacent lab to Prof Berridge at Purdue University. Dr Lin had recently unravelled the genetic sequence that encodes for a hormone called erythropoietin. Erythropoietin is released by the kidneys and stimulates red blood cell development. Using the genetic code, human erythropoietin was cloned for use in the clinic and for research purposes. For the next 10 years Prof Berridge collaborated with Amgen, the company that Dr Lin worked for, to characterise erythropoietin and understand how it interacts with various cells. During this time, Prof Berridge’s group helped make erythropoietin available in New Zealand to treat people with anaemia.
“It is very difficult to continue in one line of research for more than a decade,” says Prof Berridge. “Often times, by the end of that decade, the field has taken on a completely new direction. Discoveries in other areas of science can provide clues that branch out to eventually form a complex, multidisciplinary web.”
One of the key discoveries that came from research on erythropoietin was that chemical messengers, including hormones, growth factors and inflammatory molecules produced by our immune system, change the way our cells take up glucose, a basic molecule that our food is broken down into. The next ten years were spent looking into how glucose is transported and absorbed into the body. At a time when metabolic diseases such as diabetes were starting to become more prevalent, this research contributed to our understanding of how glucose is absorbed by our cells and how hormones, growth factors and immune regulatory molecules play a part in this process. This research was applied to investigate how cancer cells change their method of energy production to facilitate rapid proliferation.
To investigate how cancer cells deviate from the usual mitochondrial energy production, Prof Berridge and his team created an experimental model in which cancer cells were deprived of mitochondrial energy. It was at this time that Prof Berridge made his landmark discovery of mitochondrial transfer between cells. Upon making this discovery, he promptly adapted his research to become an expert on mitochondrial biology.
“It is very difficult to continue in one line of research for more than a decade,” says Prof Berridge. “Often times, by the end of that decade, the field has taken on a completely new direction. Discoveries in other areas of science can provide clues that branch out to eventually form a complex, multidisciplinary web.”
His work on mitochondrial biology established yet another research collaboration, this time a little closer to home at Victoria University of Wellington with Dr Darren Day and Professor Bart Ellenbroek. Serotonin is a hormone that acts on the brain and is thought to be a mood stabiliser. In certain conditions, including neurodegenerative diseases, depression and autism, its regulation can be disrupted, something Dr Day has been investigating. Working on a rat model in which the gene that facilitates the effects of serotonin was knocked out, he noticed decreased mitochondrial gene expression. Knowing that a mitochondria expert was just round the corner, Dr Day got in touch with Prof Berridge, sparking a new research collaboration.
“It was another field, another disease, another opportunity where we had the right tools at the right time to pursue novel research and to contribute to the field,” says Prof Berridge.
Prof Berridge and Dr Day are characterising the role of altered mitochondrial gene expression in neurological disorders.
“This is interesting because the brain continuously uses mitochondrial energy production, therefore an alteration in mitochondrial gene expression could be one of the early indications that something is wrong.” Says Prof Berridge.
They hope to uncover whether altered mitochondrial gene expression is an early marker of neurodegenerative diseases with the possibility of applying this to other disorders. This may help create tests to diagnose these conditions at an early stage where treatment is more likely to be effective.
His other current projects include investigating which genes in the mitochondria are essential for cancer cells to spread from one part of the body to another. In finding these essential genes, we may identify targets to create more effective cancer treatments that prevent cancer spread.
This ability to dynamically adapt his research according to the implications of his discoveries and the needs of society over the years is one of the key attributes that makes Prof Berridge such a distinguished researcher.
“Nothing was really too well planned. I’ve tended to follow things I found interesting and was reasonably good at, and took opportunities as they arose. Asking questions and being at the forefront of nowledge was always the driver.”
More than 50 years into his career, he is still brimming with questions and eager to know how far he can push the frontiers of biological research