Grant: Discovery Grants Program - Individual

My research program is concerned with the impact of environmental factors, such as variable temperatures or oxygen availability, on the operation of nervous systems. This research is important for at least two reasons. From a purely biological perspective, the ability to cope with these environmental factors determines the geographical ranges of different species and understanding their physiological effects allows predictions about the ecological consequences of global climate change. From a biomedical perspective, the same factors are associated with human pathology such as fever, and oxygen deprivation resulting from a stroke. At a cellular level, neural mechanisms are remarkably similar in animals as diverse as locusts and humans, so my research with insects can generate hypotheses for others to test in mammalian models.******Over the past six years we have investigated how neural performance can be tuned to optimize the trade-off between performance and energetic cost. Also we became interested in a phenomenon known as Spreading Depolarization (SD). We showed that SD occurs in insect nervous systems when they respond to extreme environmental stress by going into a protective coma. We also showed that insect SD has all the hallmarks of mammalian SD. In the next grant period we will build on these findings in the context of two general hypotheses:***1. Neural function varies in a continuum between energy-saving and high performance modes dependent upon abiotic stressors, both current and prior;***2. SD acts as an adaptive off-switch for the central nervous system when abiotic stress is extreme.******We have four objectives for the next five years. Two of these are well-defined with trainees assigned to projects. The first is to determine the role of the nervous system in setting the temperature at which insects enter a chill coma. Many insect physiologists and ecologists are interested in this but, until our recent work, all the attention has been directed at the failure of muscle function. The second is to test a potential mechanism underlying the behavioural response of adult fruitflies to low oxygen levels. The particular mechanism is shared in many different organisms, including mammals, so there will be broad interest in the results. The third objective is to determine the mechanisms underlying the reduction of neural performance to conserve energy and the fourth is exploratory to find out how specific neurons respond to abiotic stress.******My laboratory has a good record of successful training and projects are designed according to the time available and the technical proficiency of the trainees. Thus, as well as making significant contributions to our understanding of nervous system vulnerability and protective mechanisms, the research to be undertaken will train undergraduate and graduate students in difficult experimental techniques and transferable skills such as critical thinking and communication.