Postdoctoral Fellow, 1983
Professor Christine Holt FRSB FMedSci FRS joined the Laboratory of Physiology as a postdoctoral fellow in January 1983, also undertaking a Junior Research Fellowship at Worcester College. She had been awarded a 3-year MRC Training grant to work with Professor Colin Blakemore, and in close collaboration with Professor Ian Thompson, on the development of neuronal projections in the embryonic mammalian visual system. Her project investigated whether electrical activity was needed for the formation of nerve connections from the retina to the superior colliculus. Previous studies showed that visual input into the cat visual cortex failed to segregate properly into eye-specific columns when electrical activity was blocked by the neurotoxin TTX. Professor Holt and Dr Thompson used TTX to block electrical activity in the retinal neurons growing into the superior colliculus in the midbrain where they normally segregate into left-right eye specific patches during early postnatal life. They found that ‘silencing’ the ingrowing retinal axons with TTX treatment prevented the segregation from taking place. They concluded that neuronal activity plays an important role in the sorting of terminals into eye-specific territories (Journal of Comparative Neurology, 282, 1989).
Professor Holt left the Department at the end of 1983 following her marriage to Professor Bill Harris, joining him at the University of California San Diego (UCSD) to complete her postdoctoral training, where they commenced a life-long collaboration. 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 in 2003, became Professor of Developmental Neuroscience in the Department of Physiology, Development and Neuroscience.
Professor Holt’s work initially focused on the molecular guidance of axons in the visual pathway. In particular, the optic chiasm where axons make divergent choices at the midline was an area of immense interest for many neuroscientists, yet it was not understood how some axons crossed the midline, while other did not. The crossing choice of growing axons occurs during embryonic development and is an extremely important decision in setting up the proper organisation of the visual pathway. Crossing errors lead to visual impairments. The Holt lab found that a molecule called Ephrin-B was responsible for directing axon divergent choice at the optic chasm (Neuron, 25, 2000).
A second major advance from Professor Holt was the discovery of RNA translation in growing axons and its functional relevance in axon guidance and maintenance. Her paper in Neuron (volume 32, 2001) reported that the directional guidance of axons required new protein synthesis locally in growth cones. This was met with widespread scepticism as the accepted view at that time was that all proteins in axons were made in the cell body and transported out to the terminals. With the advent of increasingly sensitive molecular techniques, her lab was able to generate further evidence to support the initial discovery (Journal of Neuroscience, 30, 2010 and (Cell, 166, 2016). It is now known that thousands of mRNAs reside in axons, even in mature myelinated axons, where they are translated locally and help to maintain axon health (Cell, 148, 2012). This work holds unexpected and important relevance in neurodegenerative disease and repair.
Professor Holt’s work has been recognised by numerous awards and prizes, starting early on in her career with a McKnight Scholar Award and a Pew Scholar Award. She was elected Member of EMBO (2006), Fellow of the Medical Academy of Sciences (2007), Fellow of The Royal Society (2009) and Fellow of the Royal Society of Biology (2011). Also, in 2011, she was awarded The Remedios Caro Almela Prize for Research in Developmental Neurobiology. In 2016, she received the Champalimaud Vision Award (Portugal) and the Mabel FitzGerald Prize Lecture Medal from DPAG. In 2017, she was awarded the Royal Society Ferrier Medal. In 2020, she became an International Member of the National Academy of Sciences USA.