Decoding the Third Dimension of the Actomyosin Cortex Using Molecular Rulers: Implications for Hypoxia-Driven Cytoskeletal Remodeling in Cancer

About the Project

The actomyosin cortex is the engine of cellular architecture: a dynamic network that shapes cells, drives movement and division, and generates forces underlying tissue homeostasis and morphogenesis. In disease, particularly cancer, cells remodel their cytoskeleton to adapt to hostile microenvironments such as hypoxia, a hallmark of poorly vascularized tumors that promotes metastasis(10.1016/j.canlet.2019.01.042). Traditionally viewed as a thin two-dimensional layer beneath the plasma membrane, the cortex is now recognised as a three-dimensional structure extending hundreds of nanometers into the cytoplasm. Emerging evidence suggests it may be stratified into distinct molecular layers, influencing cellular mechanics(10.1038/ncb3525), yet testing this remains challenging. In this PhD, you will join a collaborative research environment spanning expertise in advanced imaging, hypoxia biology and cytoskeletal signalling.

You will exploit recently proposed “molecular rulers”(10.1016/j.str.2023.02.002) and super-resolution microscopy to determine how signaling molecules are positioned across the cortex’s third dimension and how this architecture is remodeled under hypoxia.

Aim1: Super-resolve the cortex’s third dimension. Kinases of the DMPK family contain extended coiled-coil domains that may function as molecular rulers to position catalytic activity at defined distances from the membrane. Our preliminary data indicate this spatial arrangement could influence actomyosin cortex organization (10.1101/2023.10.27.563985). Yet, the multilayer positioning of DMPK catalytic sites and its role in regulating cortex architecture remain unclear. Using single-molecule and light-sheet microscopy(10.1038/s41467-017-02563-4) in Wollman’s lab, you will map DMPK catalytic domains and actomyosin cortex at nanometer resolution to define their organization and propose how catalytic positioning could shape the cortex.

Aim2: Molecular rulers to stratify the cortex. Distinct signaling depths of molecular rulers may organize cortical stratification, while cortex thickness may influence their function.To test these hypotheses, in the Rodriguez’s lab you will systematically alter DMPK coiled-coil lengths with CRISPR/Cas9 and assess effects on downstream signaling and cortical actomyosin architecture in embryonic cells with varying cortex thickness. To complement cell-based studies, actomyosin networks on lipid bilayers will be reconstituted to test how catalytic positioning regulates the cortex physical properties.

Aim3: Cortex stratification under hypoxia. Hypoxia remodels the actomyosin cortex and promotes metastasis in cancers, yet this remodeling or its impact to cortex stratification has not been observed in vivo at super-resolution. A super resolution microscope integrated with Ortmann’s lab hypoxia chamber will allow you to perform this task. You will also determine how hypoxia alters the positioning and activity of ROCK, a DMPK kinase emerging as a mediator of hypoxia-induced cytoskeletal remodeling.

This project will reveal how three-dimensional organisation of the actomyosin cortex controls cellular mechanics in health and disease, while providing excellent training for careers in academia, biotechnology or quantitative biomedical research.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.

HOW TO APPLY

Please complete the following application form – Google Form

Applicants can only apply for 1 project; any additional applications will not be accepted.

Applicants should send the following documents to FMSstudentships@newcastle.ac.uk:

• a CV (including contact details of at least two academic (or other relevant) referees).
• a Cover letter – stating your project choice, as well as including additional information you feel is pertinent to your application.
• copies of your relevant undergraduate degree transcripts and certificates.
• a copy of your IELTS or TOEFL English language certificate (where required)
• a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE

Please submit your documents in the following format only:

• each document should be submitted as a separate attachment and should be named as follows: candidate surname, candidate name – document type. For example: Jones, Jamie – CV; Jones, Jamie – cover letter.
• Please submit .pdf documents where possible for your CV, cover letter, transcripts and certificates. Do not submit photos of certificates.
• Do not combine documents into one pdf. You may zip separate documents into a zip file to send via email if required.
• When emailing your application, please use the email subject header: FMS PhD Application 2026

Applications not meeting these criteria may be rejected.

Informal enquiries may be made to the lead supervisor of the project you are interested in.

The deadline for all applications is 12 noon BST (UK time) on Wednesday 20th May 2026