As of January, Dr Payam Gammage's lab begun their NIH MERIT R37 Award with the National Cancer Institute in the US. This award, held jointly with the lab of Dr Ed Reznik at the Memorial Sloan Kettering Cancer Center, will allow the team to define the function of complex I truncating mutations in cancer. Complex I mutations are particularly abundant in colorectal, thyroid and kidney cancers and, alongside a range of other mitochondrial DNA mutations that are present in ~60% of all cancers in total, remain poorly understood. The award is worth ~$4.5M over 7 years (2023-2029) and the team will be split evenly between Glasgow and New York.
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Vasileios Papalazarou is joint first author on ' Collagen VI expression is negatively mechanosensitive in pancreatic cancer cells and supports the metastatic niche', published in JCS.
Dominika Kowalczyk and her Glasgow colleagues continued their work into the ubiquitination and degradation pathway of the tumour suppressor p53. In their recent article in Life Science Alliance, they described an intramolecular interaction between MDM2 and the tumour suppressor p14ARF that partially blocks the E2 binding site of MDM2 and therefore inhibits the MDM2-p53 signalling axis.
In their study in Nature Metabolism, Emily Kay, Sara Zanivan and co-authors found that extracellular matrix production by cancer-associated fibroblasts - which is pro-tumorigenic - is under strict metabolic control, in particular as a result of increased proline synthesis.
The team, which is led from Rutgers Cancer Institute of New Jersey, Weill Cornell Medicine and Cold Spring Harbor Laboratory, will receive £20m to take on the challenge of cancer cachexia, the debilitating wasting condition responsible for up to 30% of cancer-related deaths.
Vasileios Papalazarou, James Drew and Beatson colleagues made a pre-print available that lends further evidence towards the idea that cancer cell behaviour can be influenced by sensing mechanical cues from the environment. Notably, pancreatic cancer cells, in response to a softer culture substrate, reprogrammed their gene expression, releasing factors to alter their own surroundings. In particular, the scientists found that the upregulation of collagen-VI and changes to the extracellular matrix ultimately encouraged the migration and invasion of these cells.
Today the MRC National Mouse Genetics Network is announcing a multi-million pound backing of mouse genetics for disease modelling. It will capitalise on the UK's international excellence in the biomedical sciences, creating 7 challenge-led research clusters.
Scientists as the camerawomen and -men of the unknown is the motto of a recently founded educational project. Bringing together art and science, Cell Worlds now stages an immersive experience in Bordeaux, France of the microscopic world of the human body – told through state-of-the-art fluorescent images by expert scientists like Dr Anh Hoang Le and Prof Laura Machesky at the Beatson.
We would like to extend a warm welcome to Dr Tom MacVicar, who recently took up a junior group leader position at the Beatson. Tom has joined us from the Max Planck Institute for Biology of Ageing in Cologne to establish his first independent research group here in Glasgow.
In the Journal of Medicinal Chemistry, Tamas Yelland and Esther Garcia presented a novel, alternative KRAS targeting strategy - tagging it for relocation to the cytoplasm. While sustaining KRAS binding to the protein PDE6D, KRAS moved away from its usual site of action at the cell membrane, leading to reduced downstream KRAS-oncogenic signalling. As the levels of the two proteins naturally vary between cell types, further study is required to develop a KRAS:PDE6D stabiliser that could be used as a successful anti-cancer therapy.
SCOTS scientists are set to receive a major cash injection from Cancer Research UK.
Translation, a process during protein synthesis, could be a potential target for anti-tumour therapy in colorectal cancer (CRC), as suggested by John Knight and colleagues in their recent study – 'Rpl24Bst mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K'. They investigated an impairment of the protein production machinery, a mutation in the ribosomal subunit Rpl24, in a KRAS- and APC-driven model of CRC - not only did this reduce the overall rate of protein production within tumours, but it also affected tumour growth and development. When studying human tissue, the same signalling pathway, centred around the eEF2 component and its activation, was identified in tumour samples, and hence, its proposed role as a drug-relevant pathway.
From April, Scotland will become one of seven Cancer Research UK Centres across the UK. The funding provided will help translate cutting-edge discoveries from laboratories in Edinburgh and Glasgow, including those at the Beatson, into direct benefits for cancer patients.
Great to hear about Prof Karen Blyth's experience of women in STEM as an editor for an Elsevier journal.
Six editorial team members of Gene, including Karen, were interviewed about the journal, their careers and the role of women in science: https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/editor-spotlight-meet-the-women-behind-leading-genetics-journals
At the Beatson Institute, we are fortunate in being supported by some outstanding core services. These include our Histology Service, which is managed by Colin Nixon who was recently interviewed for a Spotlight in Science article. This feature provides a great opportunity to find out about Colin's career path to his current role and the exciting work his team is doing.
Beatson Director Owen Sansom and postdoctoral fellow Arafath Najumudeen have been featured in Cancer Grand Challenges' annual progress magazine, Discover – a celebration of the advances against cancer that can be made when diverse, global teams come together and think differently.
The discovery in the 1970s that certain proteins are ubiquitinated before degradation was awarded the 2004 Nobel Prize in Chemistry. Ubiquitination has increasingly been recognised as important in various cell functions. Its best-known function is as a mediator of protein degradation: the tagging of a protein with ubiquitin marks it for degradation by the proteasome.
Together with other Beatson scientists, Joseph Hodgson and Jean-Philippe Parvy added to the expanding field of cancer cachexia [Drosophila Larval Models of Invasive Tumorigenesis for In Vivo Studies on Tumour/Peripheral Host Tissue Interactions during Cancer Cachexia]. In fly larvae models, they showed that cancer-associated tissue wasting was unrelated to food intake and tumour size, but instead was dependent on the genetic make-up of the tumour. Their findings led them to develop a new model system for cachexia where tumour and muscle can be manipulated separately. This will aid further insights into tissue interactions.
Neutrophils – which are associated with poor outcomes in cancer – come in many different types. Reliable cell surface markers are needed to distinguish and study these different populations of neutrophils. In a study released in bioRxiv (Maturation, developmental site, and pathology dictate murine neutrophil function), Postdoc John Mackey identified a protein called Ly6G as one such marker. Importantly, having an abundance of cells expressing medium levels of Ly6G was associated with higher rates of metastasis. The team also identified that the site where neutrophils develop – either the bone marrow or the spleen – affects the genes they express and their functional capacity.
The CRUK Beatson Institute is committed to promoting equality, diversity and inclusion (EDI) within our community. We value equity in our actions and deeds, diversity and inclusion within our workforce and collaborators, and the diversity of thought this brings. Read more about our vision and aims for EDI here, including our leading family friendly policies on maternity and shared parental leave.