Quick Project Snapshot
Investigating interneuron migration and placement into cortical circuits
The cortex is comprised of two neuronal populations, the excitatory pyramidal neurons and the inhibitory interneurons that modulate this excitatory output. The balance between excitatory and inhibitory neuronal activity is required for normal function and any disruption to this balance can give rise to abnormal cortical processing. Increasing evidence suggests that there is a decrease in the number of interneurons detected in post-mortem samples of patients suffering from epilepsy. Any irregularities in interneuron production, positioning or activity within the cortex have been implicated in a number of psychiatric disorders such as epilepsy, schizophrenia and autism. Despite the advances in the treatment of seizure disorders, medically intractable epilepsy requires surgical treatments. The concept of treating seizures by grafting inhibitory interneurons is more than a decade old, but has gained momentum recently due to our greater understanding of interneuron development, specification and function. The purpose of this project is to examine the ability of transplanted interneurons to integrate into a host cortex. It aims to test whether this is dependent upon two key factors: the age of the donor interneurons and the age of the host/recipient cortical tissue. Techniques to learn during this project include, surgical procedures, tissue processing, immunohistochemistry, microscopy and high-resolution real-time confocal imaging. The Brain Development and Regeneration division at the Florey Institute of Neuroscience and Mental Health investigates how neurons are generated and assemble to form the cerebral cortex. This part of the brain is responsible for originating the complex motor, sensory and cognitive functions in mammals and its assembly during development occurs through a series of highly coordinated events. We aim to identify genes involved in this process, particularly on how individual neurons are born, change shape, migrate and adopt different neuronal identities that are essential for cortical function. Our studies disclose new information on how genes have shaped brain evolution and help explain the cellular basis of neurological and psychiatric disorders.
Exosome Biology Laboratory
Brain cells are in constant communication with each other for transmitting electrical and chemical signals during mental activity. However, we believe that certain chemicals are also exchanged between brain cells for purposes that are not related to sensory and motor activity, for example for brain repair after injury. Brain communication is also important for protection of nerve cells against brain stress. We are currently engaged in discovering the nature of these communications and the circumstances behind their transmission.
We have been engaged in studying this natural method of communication using vesicles called exosomes. The exchanged material contains important messages (proteins, nucleic acids) that can have important consequences for cells that receive them. For example, in cancer, the spread of cancerous cells can be either hastened or retarded depending on the nature of these messages. Recently, we found out how to include certain additional messages that are normally not found in these exosomes. We are excited to study how these new messages can be used to repair brain cells after injury by boosting levels of repair proteins. In addition, we are enthusiastic about using these exosomes for transferring anti-cancer messages into brain tumours for reversing cancerous growth.
All Projects by this LabInvestigating interneuron migration and placement into cortical circuitsControl of protein transport in exosomes by Ndfip1How can Ndfip1 reduce brain damage following stroke?How does the brain protect itself during injury?Protein trafficking in neurodegenerative diseases.
Brain Development & Regeneration
Our group is interested in the self-defence mechanisms that operate in the brain when something goes wrong. This may take the form of degenerative disease (Parkinson's, Alzheimer's) or cancer (brain tumours) due to gene mutations and ageing. As a result, mutant or toxic proteins accumulate in brain cells, causing them to degenerate or proliferate. We have been working with one system of self-defence called protein ubiquitination which allows harmful proteins in brain cells to be removed and in the process, halt or reverse the disease process. We are particularly interested in finding how to accelerate beneficial ubiquitination in neurones using the Nedd4/Ndfip1 proteins. Our studies so far demonstrate that these proteins can halt cell death following injury and stroke, and slow down the division of brain cancer cells.