Christine Holt
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Christine Elizabeth Holt FRS, FMedSci (born 28 August 1954) is a British developmental neuroscientist. She has been Professor of Developmental Neuroscience, University of Cambridge, since 2003 and a Fellow of Gonville and Caius College, Cambridge University, since 1997. Holt is best known for her work in understanding the "basic mechanisms that govern how the vertebrate brain becomes wired up in the highly specific and complex way that it does." In 2009, she was part of an international team that received a Human Frontiers Science Program grant to develop molecular probes that will help researchers better understand the "cellular GPS" system that guides neurons to create a properly wired nervous system." Her research provides leads for future therapies for nerve damage and neurodevelopmental disorders.


Scientific career

In 1977, Holt received her Bachelor of Science (Honors) in biological sciences from the University of Sussex. She did her doctoral work under the mentorship of John Scholes at King's College London, receiving her Ph.D in Zoology in 1982. From 1982 to 1986, she was a postdoctoral fellow in the Physiology Department at Oxford University and the Biology Department of the University of California San Diego (UCSD) under the mentorship W.A. Harris and Colin Blakemore. In 1986, she became an assistant research biologist and lecturer at UCSD, where she continued to study the frog visual system in its early embryonic period. She received
McKnight Scholar Award
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for this work in 1986 and an
Alexander von Humboldt award The Humboldt Prize, the Humboldt-Forschungspreis in German, also known as the Humboldt Research Award, is an award given by the Alexander von Humboldt Foundation of Germany to internationally renowned scientists and scholars who work outside of G ...
in 1987. She joined the faculty at UCSD in 1989. During this period, she studied the mechanism in which cells from the retina grow towards and make connections with specific brain cells, performing experiments to understand the role of
adhesion molecules Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
in
axon guidance Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they mana ...
. Specifically, she assessed the loss of N-cadherin and integrins, two of the three types of adhesion molecules, on the embryonic brain. In 1991, she was named
Pew Scholar
In 1997, she moved to
Gonville & Caius College Gonville and Caius College, often referred to simply as Caius ( ), is a constituent college of the University of Cambridge in Cambridge, England. Founded in 1348, it is the fourth-oldest of the University of Cambridge's 31 colleges and one of t ...
at the University of Cambridge. In 2003, she became a Professor of Developmental Neuroscience in the Department of Physiology, Development and Neuroscience, the position she still holds today. She was elected a member of the European Molecular Biology Organization in 2005, a fellow of the Academy of Medical Sciences in 2007, and fellow of the Royal Society in 2009. In 2011, she was awarded the Remedios Caro Almela Prize for Research in Developmental Neurobiology. In 2016, she was part of a team awarded the António Champalimaud Vision Award, along with John Flanagan of Harvard Medical School, Carol A. Mason of Columbia University,
Carla Shatz Carla J. Shatz (born 1947) is an American neurobiologist and an elected member of the American Academy of Arts and Sciences, the American Philosophical Society, the National Academy of Sciences, and the National Academy of Medicine. She was th ...
of Stanford University. In 2017, Professor Holt was awarded the Ferrier Medal and Lecture by the Royal Society "for pioneering understanding of the key molecular mechanisms involved in nerve growth, guidance and targeting which has revolutionised our knowledge of growing axon tip." In 2022 she received the Rosenstiel Award. Christine Holt was elected Member of the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
in April 2020.


Research

Holt's early career was spent studying cell movement during eye development in the frog visual system. Her seminal dissertation work was published in '' Nature'' 1980. Much of what we currently know about the cellular and molecular mechanisms involved in establishing and sculpting the patterns of retinal projections comes from the work of Holt and her colleagues. Today, her research interests continue to lie in the mechanisms of
axon guidance Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they mana ...
and synaptic specificity in the development of complex brain networks. Holt is credited as the pioneer of the idea that proteins synthesize and degenerate at a local level in an axon's cone of growth. This process is required for accuracy in brain cell growth proper orientation. In addition to studying N-cadherin and integrins, she has also investigated the role of
ephrin Ephrins (also known as ephrin ligands or Eph family receptor interacting proteins) are a family of proteins that serve as the ligands of the Eph receptor. Eph receptors in turn compose the largest known subfamily of receptor protein-tyrosine kinas ...
s in axon growth and the formation of the optic chiasm. In addition, her studies have found that
netrin-1 Netrin-1 is a protein that in humans is encoded by the ''NTN1'' gene. Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon gui ...
, DCC, and laminin-1 are key players in axon guidance from the retina. For example, netrin-1 is both a chemoattractant and a chemorepellent for many classes of axons, and Holt's 1997 study shows that the growth cone of spinal neurons is chemoattractive to netrin-1 yet chemorepulsive when
cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
is present. Currently, Holt collaborates with the lab of Giovanni Armenise at Harvard University, focusing on the role of microRNAs and non-coding RNAs in axon regrowth and wiring, and as a possible link to cancer of the nervous system.


Personal life

Holt is married to W.A. Harris (FRS). Beyond teaching and research, she listed her other interests as “wildlife, walking, music, family”.


Further reading

"The Amazing Axon Adventure" http://www.cam.ac.uk/research/features/the-amazing-axon-adventure


References

{{DEFAULTSORT:Holt, Christine 1954 births Living people Alumni of the University of Sussex Alumni of King's College London British neuroscientists British women neuroscientists Female Fellows of the Royal Society Fellows of the Academy of Medical Sciences (United Kingdom) Fellows of Gonville and Caius College, Cambridge Place of birth missing (living people) Academics of the University of Cambridge Members of the European Molecular Biology Organization Vision scientists Women vision scientists