NEWS
Medicines Discovery Catapult and ZEISS focus on advancing microscopy
Medicines Discovery Catapult (MDC) and ZEISS have joined forces to improve drug discovery and early development of complex medicines by harnessing the power of advanced microscopy solutions. Advanced microscopy techniques have
emerged as a foundation of biomedical research, capable of visualising cellular functions at very high resolution, while being minimally invasive to the cells or tissues of interest. Incorporating advanced microscopy techniques into the early stages of the drug discovery process can provide invaluable information about drug activity within complex disease models. Combining MDC’s expertise in cell biology and drug discovery with ZEISS’s microscope instrumentation and image analysis capabilities, the partnership will drive the application of advanced microscopy workflows (eg confocal, lightsheet, multiphoton and super-resolution microscopy) to measure the interaction between drug molecules and biological systems, and develop assays specifically tailored to drug discovery. ZEISS is an international technology company and producer of microscopy hardware and software solutions with a
market-leading portfolio of light, electron and X-ray microscopy solutions as well as accompanying software solutions for acquisition, analysis and workflow automation. MDC is reshaping the UK’s medicines discovery industry, transforming great UK science into better treatments through partnership. It works to tackle industry-led challenges, overcoming the barriers that limit today’s drug discovery with effective interventions and industrialising new technologies to drive the adoption of new scientific tools and techniques for discovering medicines.
Aligned to this mission, MDC has established specialist advanced microscopy capabilities within its state-of-the-art Alderley Park-based laboratory facilities, utilising several ZEISS microscopes to answer drug discovery questions by applying a range of advanced microscopy solutions.
Building upon that relationship, this collaboration allows MDC to develop a unique advanced microscopy capability for drug discovery while informing the industrial
application and future development of ZEISS instruments.
Pivotal to the collaboration is a joint
project to develop advanced microscopy methods for analysis of complex medicines. Assessment of cellular internalisation, to ensure that a lead molecule can enter the cell and deliver an effective response, is a critical step in the development of complex medicines. In the project, MDC and ZEISS will produce a live-cell imaging and image analysis pipeline that can be deployed to assess novel drug delivery technologies and therapeutics, enabling innovators to advance their projects.
www.zeiss.co.uk
Unravelling the genetic mechanism behind tumour formation
New research published recently in the journal Nature offers new opportunities to improve diagnostics and targeted therapy for many cancer patients. Genetic alterations in the FGFR2 gene occur in various cancer types and represent a promising target for therapies. However, clinical responses to available therapies remained variable and unpredictable, making it difficult to select patients who would benefit from these types of treatments. An international team of researchers led by Jos Jonkers, group leader at the Netherlands Cancer Institute and Oncode Investigator, has now elucidated the mechanism behind this variation in treatment response. The results highlight the importance of studying the functional consequences of genetic changes in tumours.
In various types of cancers – including bile duct cancer, gastric cancer and breast cancer – copy number alterations
and fusions in the fibroblast growth factor receptor 2 (FGFR2) gene are relatively common. But just how these genetic variations contribute to the formation of tumours was unclear. Besides this, targeting FGFR2 with therapies brought variable and unpredictable results. But now the team led by Oncode Investigator Jos Jonkers took a data-driven approach to solve this puzzle presented by FGFR2. “The story of our new findings began over a decade ago,” said Jonkers, who is a group leader at the Netherlands Cancer Institute. “By using a mouse model in which we could induce genetic alterations in a controlled manner, we observed a specific variation in the last part of the FGFR2 gene leading to the presence of an incomplete FGFR2 protein. Follow up mouse experiments then showed that this truncated form of FGFR2 leads to the formation of tumours.”
In parallel, the team started looking for evidence of the presence of this truncated
WWW.PATHOLOGYINPRACTICE.COM SEPTEMBER 2022
form of FGFR2 in human cancer samples. With the datasets available at the Hartwig Medical Foundation and Foundation Medicine, they uncovered that many of the known alterations in the FGFR2 gene lead to the expression of the truncated protein. “We found data confirming our model at the genetic level, but also at the gene expression level,” postdoctoral fellow and first author Daniel Zingg explained. “Existing diagnostic approaches usually focus on the increased amounts of the protein in tumour samples. What we uncovered now is that it is not the amount of FGFR2 causing cells to become cancerous, but the expression of the truncated form. Tumour formation is not caused by more of the normal protein, but by a little bit of the truncated protein.” The full article can be accessed via the
link below.
www.nature.com/articles/s41586-022- 05066-5
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