Professor Christine Holt

  • Professor Emerita of Developmental Neuroscience
  • Fellow of Gonville and Caius
Professor Christine Holt

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About

Christine Holt received a BSc Hons degree in Biological Sciences from the University of Sussex in 1977 and a PhD degree in Zoology from King’s College, London University in 1982. She did her postdoctoral training in the Physiology Department at Oxford University where she was also a Junior Research Fellow at Worcester College, and in the Biology Department at the University of California San Diego (UCSD). In 1992, she joined the faculty at UCSD and became a tenured Associate Professor in 1996. In 1997, she moved to the University of Cambridge as a Lecturer in the Anatomy Department and a Fellow of Gonville and Caius College. In 2003 she became the Professor of Developmental Neuroscience in the Department of Physiology, Development and Neuroscience. She was a Pew Scholar and a McKnight Scholar in her early career and has been the recipient of numerous grant awards from the NIH, MRC, HFSP and Wellcome Trust and ERC Advanced Grant. She has served on various Scientific Advisory Boards, Editorial Boards and Selection Committees. In recognition of her research, she was elected a Member of EMBO (2006), Fellow of the Medical Academy of Sciences (2007), Fellow of The Royal Society (2009), Fellow of the Royal Society of Biology (2011), Honorary Fellow of Worcester College, Oxford (2019) and International Member of the National Academy of Sciences, USA (2020), Honorary Member of the Physiological Society (2021). She has been awarded several international prizes: the Remedios Caro Almela Prize for Research in Developmental Neurobiology (2011), the Champalimaud Vision Award (2016) and the Royal Society Ferrier Medal (2017), the Rosenstiel Award (2022), and the Brain Prize (2023).

Christine Holt became Professor Emerita in 2019. She remains actively engaged in science-related endeavours. She is not accepting applications for summer internships or research studentships.

Research

Wiring the brain: RNA-based mechanisms of axon guidance and maintenance

Christine Holt is a Developmental Neuroscientist who studies how nerve connections are formed and maintained in the brain. In the vertebrate visual system, neurons in the eye extend axons over long distances to find their synaptic targets in the brain. This impressive navigational feat, which occurs during embryonic development (before birth in humans), underlies the precise wiring of the mature brain and is essential for building functional nerve connections. The goal of her research is to understand the molecular and cellular mechanisms that guide and maintain axons. She uses multidisciplinary approaches such as in vivo gene transfer, growth cone chemotropic assays, time-lapse and single molecule imaging and genome-wide analysis in vertebrate model systems

(Xenopus, zebrafish and mouse). She has focused on particular ‘steering points’ within the visual pathway where axons alter their direction of growth, such as the optic chiasm and the optic nerve head. Her group developed one of the first in vivo gene transfer/expression approaches (1990) and found that ephrin-B is important in regulating the divergent routing of axons at the chiasm and in retinotectal map formation. Her group also identified molecular pathways important for axon growth and target entry and showed that netrin-1/DCC/laminin-1 interactions play a key role in directing axons out of the eye. In 2001, her group discovered that the growing tips of axons, the growth cones, rapidly synthesize and degrade new proteins in response to guidance cues and that inhibition of axonal protein synthesis, or degradation, blocks directional guidance. Since then her studies have focused largely on local translation and mRNA localization in axons. Her group used laser-capture technology to reveal that hundreds of mRNAs reside in axons and growth cones and went on to show that the localised synthesis of specific proteins, such as beta-actin, is required for axon turning and branching. Her group developed a subcellular genome-wide approach to investigate the mRNAs translated in axon terminals in vivo (Axon-TRAP-RNAseq) and showed that thousands of mRNAs are translated in both growing and mature retinal axons. Her group also provided some of the first evidence to show that axons are kept alive in vivo by the local synthesis of new proteins that help to sustain mitochondrial function (2012), opening new approaches to neurodegeneration. Her recent work provides novel evidence that ribosomes can be modified in axons by incorporating newly synthesized ribosomal proteins suggesting the possibility that ribosomes can be repaired locally, and possibly ‘tuned’ for optimal translation. By studying the cell biology of axons her work aims to gain a better understanding of how nerve connections are first established and how they are sustained throughout the lifetime of an animal. Fundamental knowledge of this sort is essential for understanding neurodevelopmental and neurodegenerative disorders and for developing clinical therapies in nerve repair.

 

Main sources of research funding: 

Collaborator/ colleagues

  • Bill Harris (PDN, Cambridge)
  • Julie Qiaojin Lin (Guangzhou University, China)
  • Clemens Kaminski (Department of Chemical Engineering and Biotechnology, Cambridge)
  • Hosung Jung (Yonsei University College of Medicine, Seoul)
  • Nicholas Clifton (University of Exeter Medical School)

 

Translation of beta-actin in axon terminal in brain. 

Timelapse movie of RNA granules (white) and new beta-actin protein (coloured) in a retinal axon terminal in the brain of Xenopus. New protein appears to be 'painted' by mRNA granules where translation is occurring. (Hovy Wong).