Christine E. Holt

Born: August 28, 1954 | Wylam, GB
Photograph of Christine E. Holt

Christine E. Holt was born in Wylam, England. She attended the University of Sussex, where she worked with John Maynard Smith and Michael F. Land, who encouraged her to undertake graduate studies. She received a Science Research Council fellowship and worked with John H. Scholes at the Medical Research Council (MRC) Cell Biophysics Unit, unifying her interests in genetics and neurobiology. William A. Harris introduced her to using an electrophysiological mapping system with Xenopus, after which she decided to undertake her postdoctoral studies with him at the University of California, San Diego. Her research focused on disproving the mechanospatial theory of brain development and contributing to the reaffirmation of Roger W. Sperry's chemoaffinity theory. She eventually earned a professorship at UCSD, where she remains.

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Interview Details

Interview no.: Oral History 0628
No. of pages: 119
Minutes: 300

Interview Sessions

Steven J. Novak
25-27 October 1995
University of California, San Diego, San Diego, California

Abstract of Interview

Christine E. Holt was born and raised in Wylam, a small village in Northumberland in the north of England, the youngest of three siblings. Her mother was a homemaker; her father was a naval sea captain during World War II, who then worked in the safe business and then the shipping business. She enjoyed exploring nature surrounding her home with her older brother, spending some time badger-watching, and she also played the piano. She attended British public schools (the equivalent of American private schools), and at the age of ten she was enrolled in a boarding school in which she stayed until she was sixteen. She enjoyed sports, including rounders and netball, and in school she split her focus between literature and the arts, and biology, but not other sciences; she had an interest in anthropology as well that was heightened by two trips to Africa during summer holidays. Holt's biology teacher at her college preparatory school taught with an outdated syllabus and so Holt decided to teach herself biology using Michael B. V. Roberts's textbook, Biology: A Functional Approach. She matriculated at the University of Newcastle upon Tyne to study zoology but then transferred to the University of Sussex, where she had opportunities to talk directly with professors like John Maynard Smith and was under the tutelage of Michael F. Land who encouraged her to undertake graduate studies. She received a very competitive Science Research Council fellowship for her doctoral studies and chose to work with John H. Scholes at the Medical Research Council (MRC) Cell Biophysics Unit in an attempt to unify her interests in genetics and neurobiology. At the MRC Holt faced challenges establishing Xenopus lines, though she was able to use radioactively-labeled amino acids to trace axon development. William A. Harris introduced her to the concept of using an electrophysiological mapping system with Xenopus, after which she decided to undertake her postdoctoral studies with him at the University of California, San Diego (and, subsequently, they married). Her research focus in Harris's lab was, predominantly, disproving the mechanospatial theory of brain development and contributing to the reaffirmation of Roger W. Sperry's chemoaffinity theory, which argued that every cell in the retina was specified with a different tag that matched a complementary tag in the tectum. From there she went on to another fellowship with Colin Blakemore at Oxford University to study mammalian cell development, through which she realized the impracticality of using hamsters to investigate early brain development and also the inability to demonstrate axon—tectum chemoaffinity in chicken culture. She then returned to San Diego as a researcher and, later, a professor. Soon after her fellowships and her return to San Diego, Holt and Harris spent a sabbatical with Friedrich Bonhoeffer at the Max-Plank-Institut für Entwicklungsbiologie in Tübingen, Germany, where Holt used time-lapsed video to observe Xenopus retinal axon in vivo and she investigated the possibility of guidepost cells in brain development. Soon after her return to San Diego, Holt received the Pew Scholars Program in the Biomedical Sciences award, with which she worked on developing the method of in vivo lipofection. At the end of the interview Holt talks about her work on the effects of perturbation of cell adhesion molecules on axon growth; establishing a lab; spending a year with John Gurdon at the Wellcome Cancer Research Campaign Institute in Cambridge, England; the journal review process; and balancing her career and family life and issues that women in the sciences face. The interview concludes with more of Holt's thoughts on science including the discovery that fibroblast growth factor (FGF) can prevent axons from recognizing their target; growth factor receptors' role in target recognition; and the connection of glycosaminoglycans to FGF receptor function.

Education

Year Institution Degree Discipline
1977 University of Sussex BSc
1982 Kings College, University of London PhD

Professional Experience

University of California, San Diego

1982
Postdoctoral fellow, Department of Biology
1984 to 1985
Postdoctoral fellow, Department of Biology
1985 to 1989
Assistant Research Bioogist and Lecturer
1989 to 1992
Assistant Professor-in-Residence
1992
Assistant Professor

University of Oxford

1983
Postdoctoral fellow, Department of Physiology

Max Planck Institute for Biophysical Chemistry

1986 to 1987
Visiting Alexander von Humboldt Fellow

Wellcome Cancer Research Campaign Institute, Cambridge, England

1993 to 1994
Visiting scholar

Honors

Year(s) Award
1977 to 1980

Graduate fellowship, Science Research Council

1983

Junior Research Fellowship, Worcester College, Oxford University

1983

Training fellowship, Medical Research Council

1986 to 1989

McKnight Scholars Award for Neuroscience

1991 to 1994

Pew Scholar in the Biomedical Sciences

Table of Contents

Childhood in England, College, and Graduate School
1

Family background. Childhood and early education in England. Interest in nature. Lack of good biology training at school. Teaches herself biology. Childhood and adolescent interests. Attends University of Newcastle upon Tyne. Transfers to University of Sussex. Feminism. Tutor Michael F. Land. Receivesa Science Research Council fellowship to study with John H. Scholes. Becomes interested in development of the eye. The Medical Research Council (MRC) Cell Biophysics Unit. Scholes's style of mentoring. His publication record. Advantages of working with Xenopus. Difficulties establishing Xenopus lines at the MRC Cell Biophysics Unit. Observations regarding cell migration duringeye development. Reasons Xenopus is not yet a genetic sytem. Usesradioactively labeled amino acids to trace axon devlopment. William A. Harris introduces Holt to an electrophysiological mapping system that can be used with Xenopus. Decides to pursue a postdoc with Harris at University of California, San Diego (UCSD). Develops the ability to give public presentations.

Postdoctoral Work, Positions in Europe, and Becoming Faculty in the United States
42

Well-known schoolmates. Motivation for conducting research. Options for postdoc positions. More on the decision to pursue a postdoc with Harris. Disproving the mechanospatial theory of brain development. Strategies for reducing subjective bias in experiments. Holt and Harris decide to marry. Harris's background. Accepts a fellowship to study mammalian developmentunder Colin Blakemore at Oxford University. Impracticality of using hamsters to investigate early brain development. Belief in the chemoaffinity theory of development. The quality of science at Oxford. Unsuccessful attempts to demonstrate axon-tectum chemoaffinity in chicken culture. Realizes that working at the same institution as Harris is impeding career. Holt and Harris spend asabbatical with Friedrich Bonhoeffer at the Max-Planck-Institut fiirEntwicklungsbiologie. Uses time-lapse video to observe Xenopus retinal axons in vivo. Investigates the possibility of guidepost cells in brain development. Pew Scholars Program in the Biomedical Sciences. Developing the method of in vivo lipofection. Effects of perturbation of cell adhesion molecules on axon growth. Graduate student Andreas Walz's study of glycosaminoglycans and axon guidance. Benefits of the Pew award. Establishing a lab. Lab personnel. Tenure review. Spends a year with John Gurdon in Cambridge.

Life and Research at the University of California, San Diego
82

Scientific journals. Harris's research projects. The UCSD Department of Biology. Teaching responsibilities. Funding. Writing process. Purpose of journal clubs. Quality of graduate education at UCSD. Professional duties. Journal review process. Balancing a career with family life. Women in science. Holt's and Harris's differing styles of interacting with students. Safety and otherlab issues. Discovery that fibroblast growth factor (FGF) can prevent axons from recognizing their target. Exploring growth factor receptors' role in target recognition. Interest in investigating the connection of glycosaminoglycans to FGF receptor function. Potential competitors. View of molecular biology asone of several approaches to answering biological questions.

Index
116

About the Interviewer

Steven J. Novak