Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2022 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
This 4-year PhD studentship is offered in Dr James Briscoe’s Group based at the Francis Crick Institute (the Crick).
Time is inherent to biological processes. It determines the order of events and the speed at which they take place. This is particularly obvious during embryonic development where the sequence and rate of events ensure that structures develop in the right place at the right time in a growing organism. Modifying the pace of development can affect the final size and composition of tissues. Moreover, imbalances in the speed of tissue development and stem cell differentiation can result in tissue overgrowth or deficits. Nevertheless, developmental tempo varies substantially between species. Hence understanding how the speed of developmental processes is controlled is fundamental to understanding developmental mechanism.
We are studying this question in the developing vertebrate nervous system. The same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of neurons in different vertebrate species, but the tempo at which this program operates differs between species. For example, the same developmental processes take two to three times longer in human compared to mouse, and two to three times longer in emu compared to chicken. We hypothesise that the tempo of embryonic development is controlled by genetic, molecular and cellular mechanisms that allow variation independent of the order of developmental events. The large variation in developmental speed suggests that changes in tempo might result from changes that act throughout the embryo so that the many patterning and developmental events still occur in a co-ordinated way.
To address the basis of developmental tempo we have developed quantitative assays. We have established in vitro differentiation models using embryonic stem cells of different species that recapitulate temporal differences in motor neuron differentiation. These complement and extend in vivo approaches in both mammals and avian species. To explore the molecular underpinning of developmental tempo, the project will involve measuring and manipulating factors such as cell cycle, metabolism and kinetic properties of gene expression. Comparisons between different species will provide insight into the fundamental mechanisms. To analyse the data, computational approaches will be developed to extract temporally evolving dynamics and construct mechanistic models of developmental tempo. The goal is to identify the causal relationship between molecular mechanisms and developmental tempo. Altering factors controlling developmental tempo will provide insight into the role of tempo in the generation of pattern and the control of tissue size.
Candidate background
The project offers interdisciplinary training in cutting edge techniques in stem cell and developmental biology and will provide insight into the mechanisms and principles of the gene regulatory programmes that underpin tissue development. This will contribute to understanding the development of the spinal cord as well as shed light on broad principles of embryo development.
This project would suit a candidate interested in receiving interdisciplinary training in developmental and computational biology and will involve both experimental work and data analysis.
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘INSTITUTION WEBSITE’ LINK ABOVE) BY 12:00 (NOON) 11 November 2021. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
Continue with Facebook
