Understanding Neuronal Transcription & Translation
Regulating neuronal proteins
The 2023 Brain Prize was awarded to an international group of three neuroscientists, Michael Greenberg, Christine Holt, and Erin Schuman for their pioneering research into the molecular mechanisms that regulate the neuronal proteome, the complete set of proteins expressed by neurones during development, plasticity and disease.
The researchers revealed the fundamental principles of how these processes are mediated at the molecular level – from activity-dependent gene transcription to the local translation of mRNA into new proteins in dendrites and growing axons. They showed how the synthesis of new proteins is triggered in different neuronal compartments, thereby guiding brain development and plasticity in ways that impact behavior for a lifetime. These fundamental discoveries have provided new insights into the cellular and molecular mechanisms that guide growing axons during brain development, and that enable the developing and adult brain to be shaped by experience, both in health and disease.
Michael Greenberg’s work on activity- dependent gene transcription using mammalian cells has revealed how nature and nurture cooperate to shape mammalian brain development and plasticity. Building on his early observation that neurotransmitter reception triggers the rapid induction of new gene expression, he then focused on elucidating the nature and role of neuronal transcriptional programs induced in response to extracellular stimuli. His studies have uncovered an important role for activity-dependent transcriptional responses in dynamically sculpting specific aspects of neuronal connectivity.
Christine Holt works on how connections are first formed in the brain and how they are maintained over the long term, notably in the vertebrate visual system (based on cichlid fish and xenopus tadpoles) where neurons extend over a long distance. The goal of her research has been to understand the molecular and cellular mechanisms that guide and maintain these axons. A key part of this involves local protein synthesis and degradation to guide the neuronal outgrowths. Her work has provided a better understanding of how neural connections are first established and has made the orderly growth of retinal ganglion cell axons one of the best-understood examples of axon navigation anywhere in the brain. Her work has also shed light on how axons are sustained throughout the lifetime of an animal.
Erin Schuman has been interested in molecular and cell-level biological processes that control protein synthesis and degradation in neurons and their synapses. She notably worked on rodent brain slices testing for local plasticity. The complex morphology of neurons, with most synapses located hundreds of microns from the cell body, presents a
logistical challenge for the establishment, maintenance and modification of local protein populations. Her work has been instrumental in demonstrating that neurons have solved this problem by localizing important cell-biological, protein-producing machines within dendrites and axons. Her work has fuelled the development of new technologies that have been widely adopted across neuroscience and non-neuroscience labs around the world.
More information :
https://lundbeckfonden.com/files/media/document/The%20Brain%20Prize%202023%20Information%20Pack.pdf
Last edited: 28 February 2025 16:17