Parkinson's disease research with Sonia Gandhi: stem cells, alpha-synuclein, and brain mapping at Crick and UCL

Overview

Sonia Gandhi explains how Parkinson's disease begins long before motor symptoms, with prodromal signs and progressive loss of dopamine neurons. She describes how current treatments relieve symptoms but do not slow progression, and how her lab uses patient-derived stem cells to model human brain cells in the dish. The interview also covers a pioneering brain-map project that combines single-cell data with protein-clump observations to understand the disease’s origins. Environmental risk factors, including air pollution, are discussed as potential contributors to vulnerability. Personal reflections reveal how family influences and a demanding career shape a scientist who has become a leader in neurodegeneration research.

Overview and Context

The Life Scientific interview with Sonia Gandhi covers the global impact of Parkinson's disease, the prodromal phase that precedes movement problems, and the current lack of disease-modifying therapies. Gandhi explains the disease mechanism, including the loss and dysfunction of dopamine-producing neurons and the emergence of non-motor symptoms that accompany progression.

"I wanted to address a really large unmet need" - Sonia Gandhi

From Clinic to Lab: Stem Cells and Disease Modelling

Gandhi describes how she uses induced pluripotent stem cells to turn patient skin cells back into a pluripotent state and then guide them to become midbrain dopamine neurons. This approach creates human brain models that can be studied in the lab, a major advance over traditional animal or cancer-derived cell models. The work helps illuminate how genetic and environmental factors shape disease in real human cells, enabling exploration of therapeutic strategies that slow or halt degeneration.

"I'd always known that I wanted to study the brain and within that there's a sort of plethora of possibility" - Sonia Gandhi

Unraveling the Parkinson's Puzzle: Alpha-synuclein and Mitochondria

Gandhi discusses the role of alpha-synuclein clumps and mitochondrial dysfunction as central to disease pathology. By observing how misfolded proteins form, restructure, and accumulate within neurons, researchers aim to identify early intervention points before clinical symptoms appear.

"What we really want to know is which cells are affected first" - Sonia Gandhi

Brain Mapping and Data-Driven Insights

Her team is building an interactive map of the Parkinson's brain by sequencing RNA from about a million individual brain cells from postmortem tissue, integrating this with high-resolution maps of protein aggregates. An online portal visualizes layers of information, including gene pathways and earliest pathogenic events, enabling researchers to ask targeted questions and pursue mechanistic answers through imaging and computational analysis.

"I'm feeling optimistic" - Sonia Gandhi

Environment, Community and the Future

The discussion also covers air pollution as a potential driver of neurodegeneration and the Crick Institute's role in cross-disciplinary science and pandemic response. Gandhi reflects on her journey from a shy student to a leader at a premier research center, emphasizing resilience, curiosity, and a belief in the power of collaboration to slow Parkinson's disease.

"I really do feel like I belong in a place of scientific discovery" - Sonia Gandhi