From engram to tomogram: the in situ structure of memory in the mammalian brain by cryo-electron tomography (cryoET)

We are seeking an ambitious PhD applicant that will join the Frank group to explore the in situ structure of the mouse and human brain to uncover structural mechanisms of memory and its demise in neurodegenerative diseases.

Each memory in your brain is stored by a subset of cells that are connected via synapses into a neuronal circuit, called an ‘engram’. Crucially, it is the molecular and cellular structure of the synaptic connections in neuronal circuits that are necessary for storing long-term memories. This project seeks to use advanced optogenetic labelling techniques combined with in situ structural biology (cryo-electron microscopy) to determine the structure of engram synapses and other fundamental macromolecular structures related to memory and its loss in neurodegenerative disease. 

Project objectives focussed on structural mechanisms will be tailored to the strengths and interests of the applicant and follow on the back of a string of recent successes in the Frank group, including determining the first in-tissue structure of amyloid in the mouse and human brain and post and the in-tissue molecular resolution architectures of adult mouse brain synapses (see references below) 

The PhD student would receive a broad interdisciplinary training in: i) Cryo-electron tomography and computational image processing. ii) Cryogenic correlated light and electron microscopy (cryoCLEM) of cells and tissues. iii) In vivo labelling using viral vectors and calcium imaging. Applicants from all backgrounds in natural or physical sciences are encouraged to apply. Some experience with programming (Python, Matlab or similar) would be highly advantageous. 

As a member of both the vibrant neuroscience division and Astbury Centre, this project will suit a candidate seeking a multidisciplinary training at the cutting-edge of neuroscience, biophysics, and structural biology. The University of Leeds has invested £14M in two 300 keV Titan Krios electron microscopes, a high-pressure freezer, and cryogenic fluorescence microscope, cryoFIB-SEM.

Eligibility

Applicants to this scholarship in the School of Biomedical Sciences should normally have an Undergraduate degree of 2:1 or above (or international equivalent) in a relevant subject area. A Master’s degree is desirable, but not essential. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Admissions Team prior to making an application.

The minimum English language entry requirement for postgraduate research study in the School of Biomedical Sciences is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

How to Apply

To apply for this scholarship opportunity applicants should complete an online application form and attach the following documentation to support their application.

• a full academic CV
• degree certificate and transcript of marks
• evidence that you meet the University’s minimum English language requirements (if applicable)

To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;

• Select PhD in Biological Sciences as your programme of study.
• Give the full project title and name the supervisors listed in this advert.
• For source of funding please state you are applying for a BBSRC Scholarship

If English is not your first language, you must provide evidence that you meet the University’s minimum English language requirements (below).

As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.

For further information please contact the Faculty Admissions Team:

fbsgrad@leeds.ac.uk