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Luke Thornton

Research Fellow, Faculty of Medicine & Health Sciences

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Biography

I currently work within a large, dynamic and multidisciplinary research group led by Professor Cathy Merry at The University of Nottingham in collaboration with many national and international partners forming the GlycoWeb consortium. Our aim is to further our understanding of the function and regulation of glycosaminoglycans (GAGs) in biological processes and disease using advanced non-animal methodologies to facilitate the development of new therapeutics and biotechnological applications.

May 2024-Present - Postdoctoral Research Fellow, BBSRC sLoLa GlycoWeb project at The University of Nottingham, Biodiscovery Institute

Jan 2023-May 2024 - Postdoctoral Research Scientist, CRUK Scotland Institute (formerly Beatson Institute), Glasgow

Sep 2018-Dec 2022 - PhD: 'Investigating the role of eIF4A2 in the spatial regulation of metabolic adaptation to hypoxia in colorectal cancer', The University of Nottingham, Biodiscovery Institute

Sep 2014- Sep 2018 - MSci Biochemistry & Biological Chemistry, The University of Nottingham

Other research experience:

July 2022-Sep 2022 - Professional Internship for PhD student (PIP), Developing a bioinformatic and analysis pipeline for eukaryotic mRNA-sequencing

Sep 2017-June 2018 - MSci Biochemistry & Biological Chemistry project: 'Regulation of MED13 stability through crosstalk between multiple phosphorylation pathways'

June 2016-Sep 2016 - BBSRC Research experience placement (REP): 'Regulation of Elk-3 (NET) DNA binding by mediator complex subunits'

In addition to my role as a primary researcher, I am also one of the equality, diversity and inclusion (EDI) officers for the GlycoWeb network as well as an embassador for the European Association of Cancer Research (EACR).

Expertise Summary

I have expertise in the use of secondary ion mass spectrometry (SIMS) imaging techniques including time-of-flight (ToF-SIMS) and orbitrap (OrbiSIMS) to analyse the composition and spatial arrangement of biomolecules including metabolites and GAGs within biological samples under ambient and cryogenic conditions.

I also have expertise in the development of complex, 3-dimensional cell culture models of disease and development including mouse embryonic stem cell gastruloids as models of early embryonic development as well as mouse intestinal stem cell organoids as models of advancing colorectal cancer.

Alongside this, I also have signifcant experience in CRISPR-Cas9 gene editing, RNA-sequencing, histological and immunofluorescent techniques and a wide range of analytical molecular biology techniques applicable to the areas of glycobiology and the tumour microenvironment.

Teaching Summary

I have a keen interest in sharing the knowledge and experience I have gained during my career with others both through guiding students in the lab as well as through teaching. I was a student mentor… read more

Research Summary

My current research focuses on understanding how the functional activity of glycosaminoglycans (GAGs) links to structure and how the diversity of these structures is regulated by cells. Understanding… read more

Recent Publications

I have a keen interest in sharing the knowledge and experience I have gained during my career with others both through guiding students in the lab as well as through teaching. I was a student mentor for the MSc Cancer Research & Precision Oncology students at the CRUK Scotland Institute and have also participated in the delivering of the Widening Participation summer school events held in Nottingham. I have also assisted as a lab demonstrator for both the BSc Cancer Sciences and MSc Oncology courses at The University of Nottingham as well as the teaching of critical appraisal workshops aimed at teaching students how to read, interpret and critique scientific articles.

I have supported 5 PhD students, 4 BMedSci student projects, 3 MSc Oncology students and a BSc Cancer Sciences student project as well as co-supervised two Masters project students and a Royal Microscopical Society summer student by sharing in my experiences both at a practical but also personal level to help provide the most positive experience for aspiring scientists.

Current Research

My current research focuses on understanding how the functional activity of glycosaminoglycans (GAGs) links to structure and how the diversity of these structures is regulated by cells. Understanding this will allow us to accurately predict changes in GAG composition/structure based on transcriptomic data as well as design synthetic pathways aimed at synthesising specific GAG chains that carry out a specific function. Ultimately, we aim to be able to utilise the inherent diversity of GAG biology for biomedical and biotechnological applications.

I am currently using a 3-dimensional mouse embryonic stem cell gastruloid model of early embryonic development to link GAG structure and function. Our aim is to target known biological pathways associated with GAG biosynthesis and combine this with various analytical methodologies including well-established GAG detection methods and novel time-of-flight secondary ion mass spectrometry (ToF-SIMS) to further our understanding of GAG structure/function relationships. Integrating this with novel proteomic and transcriptomic datasets generated across the developmental stages of our gastruloid model will allow us to identify key GAG regulatory components for therapeutic exploitation.

Past Research

Previously, I worked on a CRUK therapeutic catalyst grant to investigate and assess the suitability of targetting mRNA decapping enzymes of the DCP2 complex as a potential therapeutic intervention for APC-deficient colorectal cancer using CRISPR-Cas9 mediated gene editing in intestinal organoids in collaboration with Cancer Research Horizons.

During my PhD, I optimised a methodology for in situ small molecule metabolite analysis within 3-D tumour models and in vivo tissue samples using hybrid secondary ion mass spectrometry (3-D OrbiSIMS). Using this, I have studied the metabolic changes that occur across the oxygen gradient within 3-D colorectal cancer spheroids and the regulation of these changes by the hypoxia-inducible factors HIF-1ɑ and HIF-2ɑ.

Future Research

Utilising our understanding of GAG structure/function relationships to generate novel biomedical and biotechnological applications including the development of novel GAG-binding probes capable of discriminating between highly-similar GAG chains using phage display and next-generation sequencing.

Ultimately, I would like to be able to bridge my two main areas of research: glycobiology and cancer using my expertise in novel imaging mass spectrometry and GAG analytical techniques to research how the tumour microenvironment, including states of hypoxia and acidosis, influences GAG biosynthesis to alter GAG structure, and therefore function, as well as interactions with host cells to promote tumourigenesis.

School of Medicine

University of Nottingham
Medical School
Nottingham, NG7 2UH

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