Using Graph Theory and Neural Stem Cell Models to Understand Brain Network Resilience

Summary The human brain is a profoundly complex system composed of robust and efficient connections, eloquently arranged to buffer against targeted attack. This project brings together network science (graph theory) and cutting-edge stem cell technologies to uncover the mechanisms that actively counteract risk (i.e., maximise resilience) and preserve brain function following targeted attack. This project is suited to an individual with a strong computationalengineering background. Experience in either developmental neurobiology or application of high-end microscopy is desired but not essential.

Project Details

A plethora of neuroimaging studies have applied graph theory to elucidate the brain's anatomical and dynamical organisation. Graph theoretical studies show that the brain possesses small world topology—networks with intermediate randomness—which confers resilience to brain damage (e.g., vascular, neuroinflammatory, neural cell death). However, the biological mechanisms that govern network resilience remain poorly understood. This is because MRI techniques lack spatial resolution: there are ~100,000 neurons and 1 billion connections in a single MRI pixel. Neural stem cell models can revolutionise the way that we study neural network dynamics cellular and molecular mechanisms. Induced pluripotent stem cells (iPSCs) can be reprogrammed from human (bloodskin) cells obtained from selected individuals. IPSCs can be converted into neural cells and mini brains (organoids) to study neural network mechanisms ‘in a dish’.  This project will innovate tractable methods for studying the biological principles governing large-scale network organisation in the human brain, enabling widespread application in the context of health and disease. For example, this knowledge is essential to unlock the mysteries of connectopathies, including conditions such as Alzheimer's disease, schizophrenia, depression, and ADHD, which are thought reflect miswiring disorders of the brain. Successful candidates will be supervised by a multidisciplinary team embedded across two departments at the University of Melbourne: Psychiatry (computational facilities) and Anatomy and Physiology (wetlabmicroscopy infrastructure). Successful applicants will be expected to conduct research at a high level and publish in internationally recognised journals.