Development of cellular and tissue segmentation algorithms within the digital pathology platform QuPath for accurate assessment of mIF across a breadth of solid tumours.

Prof John Le Quesne, Dr Peter Bankhead, Prof Joanne Edwards

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Labs:
Le Quesne Lab
Bankhead Lab
Edwards Lab
Duration: 4 years from September 2022
Closing Date: 27th May 2022

About us

Applications are invited from outstanding candidates to join a Cancer Research UK funded PhD programme at the Beatson Institute. These are funded by the Cancer Research UK Scotland Centre, a joint initiative between Edinburgh and Glasgow which brings together cancer scientists and clinicians from across the Universities of Edinburgh and Glasgow, delivering outstanding cancer research and improved patient care. The Cancer Research UK PhD programme is integrated into the research activities of the Centre with over 80 principal investigators contributing to this cross-disciplinary programme spanning from fundamental science to translational research. Research projects benefit from state-of-the art facilities for genomics, mass spectrometry, advanced microscopy, single cell technologies, and from advanced computational and informatics capabilities.

Project description

Recent years have seen a revolution in our ability to generate high-resolution microscopic images of tumour tissue to reveal gene activity in single cells. These methods have the potential to answer a huge range of questions with relevance to basic cancer biology as well as improving outcomes for patients. In particular, advancements in multiplex immunofluorescence staining (mIF) using such technologies as POLARIS and CODEX, and in the physics of multiplex image microscopy, now make it possible to acquire microscopic images with numerous channels each of which quantifies a single gene product at RNA or protein level. The challenge is to convert these images into quantitative single-cell data for subsequent analysis using methods such as spatial statistics and artificial intelligence. The quality of the data depends upon our ability to segment images into regions (eg tumour epithelium/stroma/ necrosis/normal) and into single cell compartments (nuclei/cytoplasm/membranes). There is as yet no widely accepted transferable method to achieve this accurately. Within the CRUK Scotland Major Centre we have all the resources, physical and intellectual, required to generate a world-class segmentation algorithm which will then be used to underpin a huge range of projects within the centre. We are extremely active in the collation of patient image cohorts for biological discovery, with H&E and mIF images from many thousands of patients with common malignancies (Le Quesne/Edwards groups in Glasgow). In parallel, the Bankhead group in Edinburgh are creators of the open-source QuPath digital image analysis platform and leading experts in the development of image analytical algorithms with a particular interest in the segmentation problem. QuPath provides extensive tools to visualize and query multiplexed data, and is now one of the most widely-used platforms for digital pathology analysis (>200,000 downloads, >1,100 citations on Scopus). Deep learning artificial intelligence is being built into the QuPath code, and the successful applicant will apply AI methods to real-world tumour images to achieve optimal segmentation from image information. The project will initially focus on lung and colon cancer images, with the ambition of generating a generally applicable pan-cancer segmentation algorithm. The focus is on development of the segmentation method, but numerous biological benchmark phenomena will be quantified in the course of study, with the potential for further high-impact publications. In particular, we would bring the segmentation algorithm to bear upon active research questions around the immune microenvironment and tumour architecture.

Goals: 

  • generate a pan-cancer QuPath-based cell segmentation method (nucleus, cytoplasm, membrane)
  • generate a pan-cancer QuPath-based tissue segmentation method (malignant epithelium, stroma, necrosis, normal tissues)
  •  Validate the method across multiple tumour types and against various ground truths (eg human assessment, clinical outcomes)

Application procedure

Up to 3 studentships are available to start in September 2022 for outstanding applicants with a stipend of £19,000 p/a. These are funded by the CRUK Scotland Centre, a joint initiative between Edinburgh and Glasgow. Successful students will be registered for their degree in either Glasgow or Edinburgh, depending on the project they apply for.

We are looking for students with a very good degree in a Life Sciences subject and an aptitude for experimental work, who are also highly committed to pursuing a PhD and a career in cancer research. You should hold at least an upper second-class degree in a relevant subject and comply with English language requirements.

All applications will be administered centrally via the University of Edinburgh, please apply on the link below - this includes Glasgow-based projects with Glasgow-based supervisors: https://www.star.euclid.ed.ac.uk/public/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=PRPHDCECRC1F&code2=0020

Closing date: 27 May 2022

Interviews are expected to be held week beginning 27 June.

Applications are open to all individuals irrespective of nationality or country of residence.

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