Professor Seth Grant

Professor of Molecular Neuroscience

Background

  • 1980/1984, Graduated from Sydney University with a Bachelor of Science (Medicine) in Physiology, Bachelor of Medicine and Bachelor of Surgery
  • 1985-1989, Postdoctoral Fellow at Cold Spring Harbor Laboratory with Douglas Hanahan
  • 1989-1994, Postdoctoral Fellow with Eric Kandel at Columbia University
  • 1994, Centre for Genome Research at Edinburgh University
  • 2000, Professor of Molecular Neuroscience, Edinburgh University
  • 2003, Principal Investigator at the Wellcome Trust Sanger Institute in Cambridge
  • 2011, Professor of Molecular Neuroscience , University of Edinburgh
  • Additional appointments: John Cade Visiting Professor at Melbourne University, Honorary Professorship at Cambridge University
  • Awards: Kenneth B. Myer Award (2014), Wesley College Foundation Medal (2017), IBANGS Distinguished Investigator Award (2019), FENS EJN Award (2020)

Qualifications

BSc(Med), MB, BS, FRSE, FMedSci, MAE

Responsibilities & affiliations

Fellow of the Royal Society of Edinburgh

Fellow of the Academy of Medical Sciences

Member of Academia Europaea

Associate Member of UKDRI

Editorial board of five journals, including Neuroscience

Founder and Director of the Genes to Cognition Programme

Undergraduate teaching

Neuroscience 3

Postgraduate teaching

MSc by Research in Integrative Neuroscience

Open to PhD supervision enquiries?

Yes

Research summary

Our long-term goal is to understand the fundamental mechanisms of behaviour. We study the genes and proteins that control synapses – the connections between nerve cells. Multiprotein machines comprising many different synapse proteins are responsible for innate and learned behaviours, and their dysfunction underlies many brain diseases and neurological conditions, including Alzheimer’s disease, schizophrenia, autism, depression, addiction and intellectual disability. These mechanisms are conserved between mice and humans, opening new avenues for diagnosis and therapeutic discoveries.

Current research interests

Our current research is focussed on uncovering the scope and functional impacts of synapse diversity throughout the brain. We have developed methods for brain-wide mapping of protein composition at single-synapse resolution. These ‘synaptome’ maps, which reveal the molecular and morphological features of a billion synapses, have uncovered unprecedented spatiotemporal synapse diversity organised into an architecture that correlates with the structural and functional connectomes. We have characterised how the synaptome architecture of the brain changes throughout the lifespan, with phases of rapid expansion followed by slow decline in old age that may inform on natural ageing and windows of disease susceptibility. Importantly, we have shown that mutations that cause cognitive disorders such as autism reorganise synaptome maps. 

These new findings on synapse diversity have important implications for brain function in terms of learning and memory, leading to new models of how information is stored and recalled. We are now investigating the dynamics of the synaptome – the extent to which synapses change in the short term, during daily sleep cycles, and how rapidly synapse proteins are replaced; and, in the longer term, how sensory inputs from the environment and activity-dependent behaviour influence synaptome development. We are also unlocking brain complexity by characterising synapse diversity in the fundamental unit of the brain – the individual neuron. A major effort is progressing our laboratory, image analysis and computational tools to the direct study of the human brain, revealing the progressive impacts on the synaptome of dysfunctions such as Alzheimer’s disease. Synaptome mapping also has the potential to complement clinical techniques, uncovering what diagnostic imaging approaches such as PET tell us about damage to the synaptome. A key aim going forwards is to integrate all these synaptome data within existing large-scale international brain data resources to maximize their health discovery value. 

Research group members

  • Noboru Komiyama: Senior Lecturer
  • Emma Sigfridsson: Lab Manager
  • Malikmohamed Yousuf: Postdoctoral Fellow
  • Zhen (Ricky) Qiu : Image Analysis Developer
  • Ragini Gokhale: Informatics Engineer
  • Edita Bulovaite: PhD Student
  • Dimitra Koukaroundi: PhD Student
  • Hanan Woods: PhD Student
  • Gabor Varga: Research Assistant
  • Bev Notman: Research Assistant
  • Theresa Wong: Research Assistant

Sources of funding

The Grant lab is funded by the Wellcome Trust, European Research Council, Simons Initiative for the Developing Brain, and UK Dementia Research Institute.

Affiliated research centres

View all 104 publications on Research Explorer