'Beyond personalised and toward circuit-customised medicine: targeting molecular "Address Codes" for diverse functional neuron subtypes in the brain' with Prof Jeffrey D. Macklis

07 February 2023

Portrait of Professor Francis Szele

with Professor Francis Szele
 Associate Professor of Developmental Biology

Francis Szele focuses on discovering molecular mechanisms that regulate brain development in health and disease. In particular, he is a world expert on adult neurogenic zone developmental responses to disease and injury. He was the first to show that...

Just as people and populations are diverse - motivating ideas of personalised medicine, nerve cells - or neurons - of the brain are immensely diverse in their types and “individual” circuits that become diseased or damaged in humans. This lecture considers newly accessible molecular routes to more specific future therapies.

The long-term goals of the research to be discussed in this Stanley Ho Memorial Lecture are to understand, at a “subcellular” molecular level, controls over the initial growth - the “development" - and diversity of cerebral cortex function-specific circuitry, and diversity of mature function. The work aims to identify causes, mechanisms, and thus potential “circuit-customised” therapeutic approaches to developmental, neuropsychiatric and degenerative disease, and to elucidate and potentially overcome blocks to brain and spinal cord regeneration in disorders like spinal cord injury. The specificity, modification, and function of quite diverse brain circuitry underlies how the brain-nervous system senses, integrates, moves the body, thinks, functions with precision, malfunctions with specificity in disease, degenerates with circuit specificity, might be regenerated, and/or might be better modeled in the laboratory. However, many relevant aspects of this neuronal circuit diversity and distinctness have been inaccessible in multiple core aspects until quite recently. Understanding what actually implements and maintains circuit specificity is a key issue regarding childhood developmental nervous system abnormalities and disease, proper function vs. dysfunction in neuropsychiatric disorders, selective neuron type vulnerability of degeneration (e.g. in motor neuron disease (MND-ALS), Huntington’s, Parkinson’s diseases), regeneration (or typical lack thereof) for spinal cord injury, and investigations of disease using human pluripotent stem cell (hiPS)-derived neurons.

Professor Jeffrey D. Macklis' talk will consider possibilities of taking the idea of “personalised medicine”- tailored to an individual based on individual information - in a complementary direction– tailoring therapies to specific diseased or damaged brain circuitry.

This is the Dr Stanley Ho Memorial Lecture organised by the Oxford Martin School, Oxford Martin Programme on 3D Printing for Brain Repair and the Centre for Personalised Medicine