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 (King’s College London).
This 4-year joint Crick PhD studentship is offered in the Group labs of Dr Zena Hadjivasiliou and Dr Corinne Houart , based at the Francis Crick Institute (the Crick).
A fundamental aspect of the development of the central nervous system is the arrangement of cells along body axes during embryonic development. The highly organized specification of early neural progenitors along the dorsoventral (DV) axis of the forebrain is particularly important as it dictates the size and complexity of future cortex and basal ganglia. Understanding the mechanisms that underlie patterning of the forebrain into dorsal and ventral regional identities is essential for uncovering the evolutionary drivers of human cortical expansion. In addition, many neurological disorders, such as holoprosencephaly, epilepsy, and autism, arise from an imbalance in neuronal types. The signals controlling this organisation along the DV axis of the embryo and the downstream effectors driving differentiation and morphogenesis are broadly conserved across vertebrates, but little is known about the spatiotemporal modulation of these players across species.
This multidisciplinary project aims to understand how spatiotemporal differences in signalling networks during early brain development can lead to diversification in the course of evolution. To tackle this task, the student will use a combination of experimental assays in four organisms (zebrafish, epaulette shark, mouse and human) together with quantitative modelling. The student will examine the hypothesis that differences in timing and strength of morphogenic signals can give rise to diversity in regional patterning of telencephalon among vertebrates.
First, under the supervision of Corinne Houart, the student will develop assays to visualize and analyse the dynamics of cell behaviour and signalling activities along the dorsoventral axis in fish, mouse and human telencephalons from the onset of neural tube closure to early neurogenesis. This part of the project will combine in situ staining and analysis of transcriptome datasets from tissue, as well as mouse and human 3D cultures. The 3D cultures will be generated using biomaterial that can create opposing gradients of morphogens to mirror telencephalon patterning in vivo.
Under the supervision of Zena Hadjivasiliou, the datasets will be used to identify a restricted set of parameters describing the central components of the signalling network at play and to construct a dynamic model of spatiotemporal DV organisation. This model will aim to i) recapitulate the signalling dynamics observed in the four organisms and ii) explain how changes in signalling dynamics across evolution may lead to diverse regionalization and morphogenetic cell behaviour of the brain.
A dynamic dialogue between the experimental and quantitative aspects of this proposal will be at the core of the project. The student will therefore develop skills that will allow her/him/them to work at the interface of biology, physics and mathematics. We expect this work to deliver novel findings about the evolutionary significance of differences in signalling events on forebrain development and function and develop a practical/theoretical dynamic framework that will have a lasting impact on the field of developmental and evolutionary neuroscience.
Candidate background
The ideal candidate will have a strong interest in bridging the fields of computational/mathematical biology, developmental and evolutionary biology. This project would suit candidates with a background in physics, mathematics, computer science or engineering and a strong interest in biology, or candidates with a background in biology and willingness to develop computational and modelling skills. Some background in coding or mathematics will be beneficial for candidates with a background in biology. Due to the joint nature of the post, an open, collaborative, and highly self-motivated personality is essential.
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.
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