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Italy-Croatia-Poland-UK partnership - The GLI Transcription Factors: From Upstream Regulators to Downstream Targets

Lead Research Organisation: University of Leeds
Department Name: Sch of Molecular & Cellular Biology

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
 
Description We have developed cells able to give an accurate, simple, measure of the active or inactive state of the GLI3 protein, a key regulator of the final step in Hedgehog signalling. Through this system, we plan to discover new activators of this signals, that could serve as therapeutic targets of the next generation of specific drugs to treat some cancer types.
We have also learned key aspects of the receptor that triggers the Hedgehog signalling cascade through a visit to the Leeds group by a postdoc from Rome. The new findings are on the way for publication.
Exploitation Route The outputs so far (the grant is still active) will be used for a future research grant application in the short-term, impacting training and employability of new researchers in signal transduction with interests in preventing or treating cancer. As soon as they are published, they will help advance the careers of ECRs involved, helping them secure fellowships or lecturer positions.
The outputs are expected to lead to future PhD scholarships to continue this research, and in the longer term are expected to be used for identification of novel therapeutic targets.
Sectors Education

Pharmaceuticals and Medical Biotechnology
 
Description Strategic funding
Amount £5,288 (GBP)
Funding ID N/A 
Organisation University of Leeds 
Sector Academic/University
Country United Kingdom
Start 06/2022 
End 03/2025
 
Title GLI3 processing reporter cells 
Description We have generated and validated a reporter cell line stably expressing Nluc-GLI3-GFP to perform high throughput screening of CRISPR libraries to identify novel positive and negative modulators of GLI3 processing. 
Type Of Material Cell line 
Year Produced 2025 
Provided To Others? No  
Impact Too early to say. 
 
Description BBSRC -IPA 
Organisation Ruder Boskovic Institute
Country Croatia 
Sector Public 
PI Contribution Starting collaboration through an International Partnering Award - officially beginning in April 2022
Collaborator Contribution Partners will contribute to development of a Hedgehog signalling website resource and provide genetically modified human-derived cancer cell lines, advanced training in mass spec of GLI proteins PTMs, and transgenic mice.
Impact First Hh signalling workshop organised in January 2023 at the University of Leeds. 20 delegates attended and presented talks in a 2-day networking event.
Start Year 2022
 
Description BBSRC -IPA 
Organisation Sapienza University of Rome
Country Italy 
Sector Academic/University 
PI Contribution Starting collaboration through an International Partnering Award - officially beginning in April 2022
Collaborator Contribution Partners will contribute to development of a Hedgehog signalling website resource and provide genetically modified human-derived cancer cell lines, advanced training in mass spec of GLI proteins PTMs, and transgenic mice.
Impact First Hh signalling workshop organised in January 2023 at the University of Leeds. 20 delegates attended and presented talks in a 2-day networking event.
Start Year 2022
 
Description BBSRC -IPA 
Organisation University of Warsaw
Country Poland 
Sector Academic/University 
PI Contribution Starting collaboration through an International Partnering Award - officially beginning in April 2022
Collaborator Contribution Partners will contribute to development of a Hedgehog signalling website resource and provide genetically modified human-derived cancer cell lines, advanced training in mass spec of GLI proteins PTMs, and transgenic mice.
Impact First Hh signalling workshop organised in January 2023 at the University of Leeds. 20 delegates attended and presented talks in a 2-day networking event.
Start Year 2022
 
Description Collaboration with Dr. Pawel Niewiadomski 
Organisation University of Warsaw
Country Poland 
Sector Academic/University 
PI Contribution We have provided proteomic datasets for cross-referencing and contributed to many brainstorming sessions to guide PhD and postdoctoral researcher projects.
Collaborator Contribution The partner has contributed key unpublished data, methods and a large amount of new cell lines and plasmids for generation of preliminary data for grant applications.
Impact Nothing to report yet.
Start Year 2023
 
Description Collaboration with Prof. Lucia Di Marcotullio 
Organisation Sapienza University of Rome
Country Italy 
Sector Academic/University 
PI Contribution This collaboration to study the microenviroment of medulloblastoma tumours will use spatial proteomics expertise in house as well as functional studies of validation of Erap1 in Hh signalling. I will provide lab space, consumables support, travel and lodging, and access to spatial proteomics of mouse tissue.
Collaborator Contribution The collaborator will contribute mouse medulloblastoma tissue blocks of different phenotypes, collected by the PhD student, and dedicated time of the student to spend in my lab in Leeds as part of her PhD as well as costly antibodies. I have become officially a co-supervisor in the project.
Impact Not yet
Start Year 2024