Winchester 23 266 Beatson Lab Groups 000212

New CRUK blog post written by Catherine Winchester desribes the value of creating annual statements on research integrity. Catherine, Senior Research Advisor - Grants and Research Integrity at the CRUK Scotland Institute, explains what an annual statement on research intergrity is, what it can tell us and looks to the future of annual research integrity statements. 

Read Catherine's blog here.

New research from across the Sansom, Bushell, Le Quesne, Norman and Coffelt labs at the CRUK Scotland Institute released on BioRxiv has shown that eIF4A1 is specifically required to support the translational demands of oncogenic Wnt signalling. The team report the suppression of intestinal tumourigenesis in colorectal cancer models following loss of eIF4A1 and argue that deregulated/increased translational reprogramming should be considered a prerequisite/hallmark of cancer and not simply a marker of increased proliferation.

Piotr Dzien, Karen Blyth, David Lewis, and colleagues have published an article in Cancer & Metabolism that proposes positron emission tomography (PET) imaging of the sodium iodide symporter (NIS) as a rapid and sensitive in vivo test for metabolic treatments targeting energetic pathways. This new approach makes in vivo testing more practical, giving an immediate readout after a single dose; it reduces drug costs, animal use, and the time associated with long therapeutic studies.

Cancer Research UK have announced their biggest ever investment in Scotland which will be awarded to the Beatson Institute, now being renamed as the Cancer Research UK Scotland Institute. The funding will be up to £123 million over a seven-year period and will support around 300 researchers and 100 support staff across 30 research groups.

This investment will boost Scotland as a global hub for cancer research on an increasingly competitive worldwide stage and help the recruitment of international talent.

Professor Owen Sansom, the Director of the Institute, has said “This recognition of the hard work and determination of our researchers to find new ways to tackle cancer, as well as improve current treatments, is major boost for both future cancer patients in Scotland and for the newly titled Cancer Research UK Scotland Institute. It represents an unprecedented vote of confidence in Scotland’s scientific prowess.”

Read more here.

Owen Sansom, Director of the Cancer Reserach UK Beatson Institute, has been selected for the final stages of Cancer Grand Challenges as part of team PLASTICITY-Tx. The team will now compete to win up to $25m funding to take on one of cancer's toughest challenges.

Using a novel strain of influenza A and a modified melanoma model system, work by Chiara Pirillo, Ed Roberts and colleagues, published in ScienceImmunology, has shown that co-encoded contextual information and antigen allow resident conventional dendritic cells (rDCs) to be appropriately activated in the lymph node. By determining how immune responses may be improved by elevated rDC function, these findings have important implications on the design of cancer vaccines and immunotherapies.

Dr Johan Vande Voorde, associate scientist at the Cancer Research UK Beatson Institute, is currently working as part of the Cancer Grand Challenges Rosetta team which focuses on 3D tumour mapping at the molecular and cellular level. This month, he was interviewed by Cancer Grand Challenges about his recent work published in Nature Metabolism

Read the interview here.

 

In their recent article in Neuro-Oncology Advances, Dominik Koessinger, David Novo and colleagues identify an inter-cellular communication tool where p53-mutant glioblastoma cells release podocalyxin-containing extracellular vesicles. This stimulates neighbouring brain cells to secrete factors creating an environment favourable to cell invasion and ultimately promoting cancer cell infiltration in the brain. Investigating the tumour microenvironment in this study has potentially highlighted a druggable target for a cancer type with particularly poor prognosis.

Work – published in Molecular Oncology - by recent PhD graduate Declan Whyte from the Murphy lab described a novel role for NUAK1 in chromosome segregation and centrosome duplication during cell division. Although growing evidence has suggested NUAK1 as a potential vulnerability in cancer, in particular in conjunction with KRAS and MYC, the work raises concerns about the application of anti-NUAK1 therapies.

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.

Using a lineage tracing model, Stephanie May and colleagues established that pericentral hepatocytes played only a limited role in the regeneration of the liver. Their Axin2CreERT2 knock-in model reconciled previously conflicting reports on the involvement of this cell type and revealed methodological challenges of preclinical modelling. [Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration]

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.

In their study in Nature Communications, Dustin Flanagan, Owen Sansom and colleagues showed that high TGFβ expression – whose role has been described as contradictory in colorectal cancer – accelerated tumour formation in the context of KRAS and APC mutation. While linked to aggressive disease progression, mechanistically epithelial TGFβ activation stimulated growth factor signalling pathways which as a result is a promising finding for potential drug targeting strategies.

Shashi Singh, Peggy Paschke, Luke Tweedy and Robert Insall showed that the PKB and SKG kinases were involved in regulating the formation of cell projections and ultimately, the cells’ moving speed – mechanistically, the enzymes appeared to drive changes in the phosphorylation of the Scar/WAVE complex, which is a key driver for molecular changes at the front edge of a cell. [AKT and SGK kinases regulate cell migration by altering Scar/WAVE complex activation and Arp2/3 complex recruitment in Frontiers in Molecular Biosciences]

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.

MRC announces £2.9 million investment into furthering cancer research

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.

A new science and art project boldly takes microscopy images where they have never gone before

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.