Christine Holt
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Christine Elizabeth Holt (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 The University of Cambridge is a Public university, public collegiate university, collegiate research university in Cambridge, England. Founded in 1209, the University of Cambridge is the List of oldest universities in continuous operation, wo ...
, 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 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 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 Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the ''CDH2'' gene. CDH2 has also been designated as CD325 (cluster of differentiation 325). Cadherin-2 is a transmembrane protein expressed in multi ...
and
integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
s, 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 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 The European Molecular Biology Organization (EMBO) is a professional, non-profit organization of more than 2,100 life scientists. Its goal is to promote research in life science and enable international exchange between scientists. It co-funds cour ...
in 2005, a fellow of the
Academy of Medical Sciences The Academy of Medical Sciences is an organisation established in the UK in 1998. It is one of the four UK National Academy, National Academies, the others being the British Academy, the Royal Academy of Engineering and the Royal Society. Its ...
in 2007, and fellow of the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
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 the ...
of Stanford University. In 2017, Professor Holt was awarded the Ferrier Medal and Lecture by
the Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, r ...
"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 The Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research is awarded by Brandeis University. It was established in 1971 "as an expression of the conviction that educational institutions have an important role to play in the en ...
, and in 2023
The Brain Prize The Brain Prize, formerly known as The Grete Lundbeck European Brain Research Prize, is an international scientific award honouring "one or more scientists who have distinguished themselves by an outstanding contribution to neuroscience and who are ...
. Christine Holt was elected Member of the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, 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 ...
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 Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
'' 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 Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the ''CDH2'' gene. CDH2 has also been designated as CD325 (cluster of differentiation 325). Cadherin-2 is a transmembrane protein expressed in multi ...
and
integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
s, 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 ki ...
s in axon growth and the formation of the optic chiasm. In addition, her studies have found that netrin-1,
DCC DCC may refer to: Biology * Netrin receptor DCC, human receptor protein, and the gene encoding it * Dosage compensation complex Business * Day Chocolate Company * DCC plc, an Irish holding company * Doppelmayr Cable Car, cable car company * D ...
, 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: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...
is present. Currently, Holt collaborates with the lab of Giovanni Armenise at Harvard University, focusing on the role of
microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...
s and
non-coding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not Translation (genetics), translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally imp ...
s 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 Commanders of the Order of the British Empire 20th-century British women scientists 21st-century British women scientists