Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please could you give a brief introduction to electrophysiology?
Bioelectricity is an essential part of our make-up. All cells in our body communicate by electrical activity. If an electrical charge is applied to one of our muscles it will interpret that electrical activity as a signal telling it to contract. When doctors send patients for an electrocardiogram test, they are measuring the electrical impulses emitted by cells with every heart beat.
Electrophysiology is a technique that uses specialist equipment to measure bioelectrical currents very precisely, allowing scientists to measure the electrical activity, not of an entire organ, but of a single cell, or even a small region of a cell.
What can electrophysiology teach us about cell function?
Each cell has an outer membrane, internal fluid and multiple organelles (cell’s equivalent of organs). While the cell is a contained system, its function is altered by the signals that it receives from other cells, in the form of bioelectricity.
Electrophysiology equipment allows researchers to measure bioelectricity at the individual cell level, in order to understand how cells communicate and respond to stimuli such as drugs or toxins. These measurements of a cell’s function are made in real-time, providing information about which components of the cell respond and how quickly they respond to a stimulus.
Can electrophysiology teach us about the cellular basis of diseases?
Yes, electrophysiology is one of the most suitable techniques for these types of studies. It allows researchers to determine precisely how a disease process is exerting its effect and having a consequence for cell function. This type of information is particularly beneficial when developing suitable therapeutic treatments.
Is electrophysiology also useful for testing drug treatments?
Absolutely! Therapeutic agents often function by activating or blocking channels, pores or transporters on the surface of cells. This effectively changes the electrical activity of the cell. Electrophysiology can be used to directly evaluate how effective a drug is at activating or blocking its target, and how specific the effect is on a variety of cell types.
You have recently been reported as saying that “electrophysiology is rapidly becoming an essential component of neuroscience research”. Why do you think this is the case?
There are multiple neuroscience research groups at UTAS who are eager to use the new electrophysiology equipment, in particular the neuroscience groups of the Menzies Research Institute managed by Dr Kaylene Young, Prof David Small, A/Prof Tracey Dickson and Dr Lisa Foa.
The brain contains billions of nerve cells, yet these cells do not work alone - they form a connected network. Healthy brain function relies on information being sorted and then faithfully transferred to the most appropriate brain region. This information transfer is seen by individual brain cells as an ion flux, which is an electric current.
Some diseases cause brain cells to receive too much or too little electric input from surrounding cells. Either situation can disrupt the cell’s function, and even result in its death and removal from the network. As neuroscientists we are trying to understand the disease process, and intervene to protect and even restore brain function. Therefore it is essential that we understand how brain cells are being electrically stimulated normally, and how this changes as part of a disease’s pathology.
Also, as we better develop cell replacement therapies, and start to implement them, it is going to be very important to ensure that the new replacement cells become correctly wired into the brain network. Electrophysiology allows us to measure all of these things.
Do you think electrophysiology will also become an important component in other research fields?
All of the cells in the body communicate via ion flux (electrical current) - only the size of the current is often larger in nerve cells. Once the equipment is fully operational in the Institute, it is envisaged that the list of users will expand to include other researchers within the Institute, such as the Muscle Diabetes Research Group led by Professor Steve Rattigan, Dr Steve Richards and Dr Michelle Keske.
The University of Tasmania’s Menzies Research Institute has recently been awarded a grant from the Ramaciotti Foundations. Please could you outline how you plan to use this grant?
In conjunction with the Ramaciotti Foundation, Menzies Research Institute Tasmania aims to establish a multi-user, state-of-the-art mammalian cell electrophysiology facility. This will be the first equipment of its kind in Tasmania, and the facility will be available for use by researchers within the University of Tasmania, as well as partner organisations including The Antarctic Division and CSIRO.
What impact do you think this research will have?
The new equipment will be used for various research projects that each aim to improve human health. Four of the Menzies Research Institute Tasmania neuroscience groups plan to use the equipment as soon as it is established in the building.
Dr Young’s laboratory focuses on promoting the generation of new cells within the adult brain, and she will use the equipment to examine the ability of the newly generated cells to electrically integrate into the pre-existing circuitry.
Prof. David Small’s research aims to understand Alzheimer's Disease pathology and electrophysiology equipment will allow him to better assess how the pathology negatively affects brain cell function.
Research in Dr Foa’s laboratory aims to improve our understanding of the mechanisms that control calcium signalling (calcium ion flux), as this has direct implications for a wide variety of developmental conditions including mental retardation, autism and schizophrenia and also regeneration after injury.
A/Prof. Dickson investigates how the brain responds to trauma and disease, and has a particular interest in developing and testing novel therapeutics to determine how effective they are in preventing or slowing the progression of brain damage.
How do you think the future of research using electrophysiology will progress?
This equipment will allow us to examine aspects of cell function that would have previously gone un-noticed. Researchers are constantly finding new ways to use this technology and new applications for it in investigating what are very small cellular changes, but have very large consequences for how our bodies function.
Would you like to make any further comments?
We would like to thank the Ramaciotti Foundation for their generous support.
Where can readers find more information?
More information about the researchers at Menzies Research Institute Tasmania that will be using this equipment is available on the Institute website.
For further information on the Ramaciotti Awards: http://www.perpetual.com.au/ramaciotti/
About Dr Kaylene Young
Dr Kaylene Young was the recipient of a Sir John Monash Science Scholarship, and graduated from Monash University with a Bachelor of Science (hons) degree in 2000.
As the recipient of an Australian Postgraduate Award, she was extremely fortunate to pursue her interest in adult brain stem cell biology, by undertaking graduate training in Prof Perry Bartlett’s laboratory, at the Walter and Eliza Hall Institute (University of Melbourne), where she was co-supervised by A/Prof Elizabeth Coulson.
She spent the final 18 months of her PhD assisting in the successful establishment of the Queensland Brain Institute, at the University of Queensland, where she trained new students and staff to purify brain stem cells and maintain them in culture.
In 2004 she moved to the United Kingdom to work as a postdoctoral research fellow at University College London (UCL). Her early research in the UK revealed that there are multiple types of stem cells in the mature brain that generate a variety of different types of new nerve cells.
Following this work she was awarded an international Career Development Award in Stem Cell Research, which allowed her to remain at UCL and study a cell type called Oligodendrocyte Progenitor Cells (OPCs), which are the largest actively dividing cell population in the mature brain. She discovered that OPCs generate significant numbers of new insulating cells for the mature central nervous system, a discovery that is likely to be extremely important for future therapies aimed at treating multiple sclerosis (loss of insulating cells).
In 2011 she was appointed as a research group leader at the Menzies Research Institute Tasmania within the Neurodegeneration Division. Having successfully applied for an international project grant, she spent the eighteen months of this position learning how to make electrical recordings from brain cells, receiving expert training in her collaborator, Prof David Attwell’s laboratory (also UCL).
The Ramaciotti Equipment Grant that was recently awarded to the Menzies Research Institute Tasmania will allow the institute to purchase the equipment that is required to make these recordings. At the Menzies Research Institute they conduct a significant amount of nervous system research. Nerve cells and many other cell types require well regulated electrical activity for their function. The new equipment will be set up as a core facility and Kaylene will be training many of the staff and students to use it. They will measure the electrical activity of cells, determine how this changes as disease symptoms progress, and determine how well potential drug treatments can restore normal electrical activity to those cells.
Kaylene was recently awarded an NHMRC career development award to allow her to build the capacity of her laboratory and pass on her newly acquired expertise to others in the Institute.