Synapses are the functional units of the brain and are targets of many diseases and drugs. Synapses are specialized structures where nerve cells communicate with each other through a process called synaptic transmission. Chemical synapses, which make up the majority of synapses in the nervous system, use a process that involves the release of neurotransmitter by the presynaptic neuron and the binding of this neurotransmitter to the postsynaptic neuron or muscle. This process is regulated and modulated by many proteins and lipids. Furthermore, the ability of synapses to transmit information from one neuron to another change with experience, stress, or injury in physiological processes such as pain. These changes can be due to functional or structural modifications of synapses. Our research group is broadly interested in understanding the mechanisms of synaptic function and how changes at synapses play a critical role in the development of pain. Our two current primary research goals are to:
1. Understand the roles of lipids in regulating synaptic function and development.
2. Identify the molecular machinery that regulates nociception and determine how it is influenced by injury or stress.
We use the fruit fly, Drosophila melanogaster, as a model to address these questions, using a combination of genetics, molecular biology, electrophysiology, calcium imaging, optogenetics and behavioural approaches.
Lipid regulation of neurotransmission and synaptic structure
The long-term goals of this part of our research program are to determine how lipids contribute to the function and development of the nervous system. Specifically, we are interested in how lipids regulate synapse formation, neurotransmission, and synaptic plasticity. Lipids such as cholesterol, phospholipids and fatty acids likely play critical roles in these processes. Yet little is known about the physiological consequences of acutely altering the lipid content of membranes, how synaptic activity regulates the lipid composition of membranes, and the molecular mechanisms that are responsible for lipid trafficking and maintaining the correct lipid composition of the membranes at the synapse. Our research group uses the Drosophila larval neuromuscular junction, a well-established model system for studying synapses, to understand the roles of lipids in synaptic function and development.
Mechanisms of nociception and nociceptive sensitization
Most people are affected by pain. Nociception is a process in which pain-sensing neurons called nociceptors detect harmful stimuli and trigger a behavioural response that allows an organism to avoid potential tissue damage and death. Hyperalgesia is a condition in which individuals experience increased sensitivity to pain, in some cases due to sensitization of nociceptors. The long-term goals of the second part of our research program are to identify the molecular machinery that regulates nociception and hyperalgesia. Drosophila models of nociception can mimic many aspects of mammalian models of nociception. We use Drosophila larvae and adults as simple in vivo systems to understand nociceptor function and to screen for genes and proteins that have critical functions in nociception and hyperalgesia.
