Tom MacVicar and Vicky Cowling join the Beatson Institute

Tom MacVicar

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.
Mitochondria form the focus of work in Tom's lab. The group's goal is to understand the mitochondrial changes - in form, function and make-up – that occur during cancer development. The lab will pursue the identification of mitochondrial metabolite transporters and investigate how they aid rewired metabolic demands in support of cancer cell proliferation. Further research will concentrate on the possible translation of these findings into interventional cancer therapeutics.
"I'm delighted to join the Beatson where my team will help drive the discovery and understanding of metabolic vulnerabilities in cancer. Cancer metabolism is a key research theme at the Institute and I'm excited to interact with, and learn from, world-class cancer research groups at the Beatson and University of Glasgow. Our work will also depend on close collaboration with the fantastic research facilities available here."

Cowling Vicky 2021

We are also looking forward to the arrival of Prof Vicky Cowling, who will join the Institute in May. Vicky is relocating her research group to Glasgow from the Centre of Gene Regulation and Expression, University of Dundee.
The Vicky's lab aims to understand how gene expression is regulated in health and disease. In particular, the team is interested in the RNA cap – a structure found on RNAs that not only protects RNA but is also involved in its processing. The group's research investigates RNA cap biochemistry and regulation in development, immune cell activation and following oncogene dysregulation in cancer.
"We are delighted to be moving to the Beatson and becoming part of this vibrant and collaborative community of scientists. Researchers at the Institute are dedicated to making discoveries in human biology and advances in cancer research – we look forward to joining this effort."

Publication Highlights: Feb 2022

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.

Together with Beatson scientists, Tim Humpton (from the Vousden lab at the Francis Crick Institute) has described an easier way of tracking p53 activity. The study, published in Science Signaling, introduced a new near-infrared reporter that enables investigation of p53's role in health and disease without the need for further intervention. While confirming the role of p53 in the liver after irradiation or paracetamol treatment, further applications of the reporter will allow the study of p53 activity during tumour development, offering insights into when to attempt therapeutic intervention.

Dominik Koessinger, David Novo and colleagues made a pre-print available on bioRxiv that identified a cell communication tool involving p53-mutant glioblastoma cells releasing extracellular vesicles. Favouring the sorting of podocalyxin into these vesicles stimulated other brain cells to create an invasive environment and promoted cancer cell infiltration in the brain. This study highlighted potential druggable targets for a form of glioblastoma with a particularly poor prognosis.

In a collaborative effort led by Beatson scientists and the University of Newcastle, a pre-print on bioRxiv showed that inhibiting CXCR2 could sensitise liver cancer to immunotherapy when patients were also affected by non-alcoholic fatty liver disease. Mechanistically, the treatment switched tumour neutrophils to an anti-tumour phenotype and enhanced the response of other immune cells. This suggests anti-CXCR2 therapy might be a promising anti-cancer agent in patients with liver cancer.

SCOTTISH SCIENTISTS GET £12 MILLION BOOST FROM CANCER RESEARCH UK

Multimillion-pound investment in Scottish cancer research is welcomed by bowel cancer survivor, Iain, from Helensburgh

SCOTS scientists are set to receive a major cash injection from Cancer Research UK.

Today (Friday, February 4), on World Cancer Day, the charity is announcing that experts at the Cancer Research UK Scotland Centre will receive around £12 million over the next five years for their ground-breaking work, as part of the development of a unique chain of cutting-edge research hubs around the UK.

This World Cancer Day also marks Cancer Research UK's 20th anniversary.

The £12 million will be used to accelerate work into diagnosing and treating cancers which are among the most prevalent in Scotland, including bowel cancer, mesothelioma, liver cancer and brain tumours.

Professor Ian TomlinsonProfessor Ian Tomlinson, Co-Director of the Cancer Research UK Scotland Centre, said: "We've had a challenging year and COVID-19 has slowed us down. But we will not stop working hard to find new treatments for cancer, and this investment will give us the tools we need to deliver high quality research which will make the biggest difference for patients.
"This investment means we will be able to further develop our work in translational research – getting cutting edge discoveries from the laboratory to patients and learning as much as possible from patients to initiate new research."

Professor Owen Sansom sw9Professor Owen Sansom, Co-Director of the Cancer Research UK Scotland Centre, added:
"The new Cancer Research UK Scotland Centre will bring some of the best scientists in Scotland together to tackle some of the biggest cancer challenges that matter to people across Scotland.
"We will have a relentless focus on tackling cancers which affect our fellow citizens, drawing on expertise built up over many decades.

The Scotland Centre, comprising scientists from Edinburgh and Glasgow, has been chosen as one of just seven locations to secure funding in the latest review of the Cancer Research UK Centres network of excellence. These are world-class research centres which draw together leading research and medical expertise to drive the best possible results for cancer patients.

Every year, 33,200 people are diagnosed with cancer in Scotland*.

The multimillion-pound investment in the nation's cancer research is welcomed by bowel cancer survivor Iain Kerr, 66, from Helensburgh, who last year celebrated the arrival of his first grandchild.

Dad-of-two Iain was diagnosed with bowel cancer in January 2014 – just three months after moving home to Scotland from southwest England to retire with wife Wendy.

Then aged 58, the move meant Iain was eligible for Scotland's bowel cancer screening programme, which led to the discovery of a tumour in his lower bowel.

A keen hillwalker, Iain says when he left Vale of Leven Hospital in shock after hearing his diagnosis, he looked to Ben Lomond in the distance and thought, "Will we ever walk up there again?"

But following surgery to remove his tumour and a bowel resection – which was carried out using a surgical procedure never before performed in Scotland – Iain was told he wouldn't need any further treatment.

Welcoming Cancer Research UK's £12 million investment in the Cancer Research UK Scotland Centre, he said: "As far as I'm concerned, research and screening saved my life. The specialist surgery I had – a procedure that was carried out in Scotland for the first time – that's down to research.

"If I had been diagnosed with cancer twenty years ago, the outcome might not have been the same for me. I'm so grateful for the treatment that saved my life. I've been given the greatest gift of all – more precious moments with my loved ones, including meeting my beautiful granddaughter, Jasleen."

Iain continued: "I was lucky enough to avoid chemotherapy, but not everyone is as fortunate as I was. It's fantastic news that Cancer Research UK is investing £12 million in this new research centre in Scotland and bringing together the country's top experts from Edinburgh and Glasgow. I hope that this new funding and collaboration will lead to better, kinder treatments for people with bowel cancer, and other cancers impacting the lives of people across Scotland."

Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said:

"This past year proves, more than any other, the value of investing in science and medical research, and what can be achieved with collective focus and collaboration. Just like science is our route out of the pandemic, science is our route to beating cancer.

"Despite the impact of the pandemic on the charity's income, we are funding some of the best and most promising research in Scotland to help more people survive.

"Survival rates have doubled since the early 1970s and Cancer Research UK's work has been at the heart of that progress. Every step our doctors, nurses and scientists take relies on every pound raised through fundraising, and they need your support now more than ever.

"Our determination to beat cancer hasn't faltered and we are even more focussed on our ambition of seeing 3 in 4 people survive their cancer by 2034. One in two of us will get cancer in our lifetimes, and all of us can support the research that will beat it."

Marked on February 4, World Cancer Day is an international initiative, uniting people across the globe to take action against the disease.

For Cancer Research UK the awareness day takes on extra significance this year, as it celebrates its 20th birthday.

While the charity was formed in 2002, its history dates back to the founding of the Imperial Cancer Research Fund in 1902. Its work has been at the heart of some of the biggest developments in cancer, from radiotherapy to some of the most used cancer drugs around the world today.

And now the cutting-edge research it funds has helped lead to more people than ever in the UK surviving their cancer for 10 years or more.

Gareth-Inman-Head shot    Photo    c.gourley-2017

We also welcome the extended leadership team: Prof Gareth Inman - Chief Operating Officer (left), Dr Jackie Beesley - Centre Manager (middle), Prof Charlie Gourley - Clinical Lead (right)

Publication Highlights: Dec 2021/Jan 2022

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.

Hing Leung, Arnaud Blomme and co-authors have linked the THEM6 protein to drug resistance in advanced prostate cancer ('THEM6-mediated lipid remodelling sustains stress resistance in cancer'). In their study, THEM6 affected the lipid composition of cancer cells, thus altering theirstress response, such as that induced by anti-cancer therapy. As the researchers also observed that THEM6 created a 'tumour stimulating' environment in other hormone-dependent cancers, they propose it as a new therapeutic target beyond just prostate cancer.

The structural complex K48-linked polyUb chain, which fits under the umbrella of ubiquitin (Ub) post-translational modifications, can act as a signal to target proteins for degradation. Using chemical biology approaches, scientists Mark Nakasone and Karolina Majorek described the structure of one of these complexes, consisting of a RING E3, the E2 UBE2K and a Ub acceptor, in Nature Chemical Biology. The study revealed the function – acceptor recognition, multiple Ub binding site or recruitment of Ub substrates- of individual complex components and their domains, and thus, explained the molecular basis of ubiquitin chain assembly, which up till now has remained elusive to the field.

Work by former Beatson PhD student Valentin Barthet and members of the Tumour Cell Death lab characterised two new, but functionally distinct, members of the DRAM protein family, a set of proteins involved in the cell's clean up and recycling function. Unlike other DRAM proteins, p53 did not activate DRAM-4 or DRAM-5, but they were stimulated when nutrient supply was scarce. Although found in distinct locations within the cell, the endosome and plasma, respectively, DRAM-4 and DRAM-5 had compensatory effects on autophagy and cell survival. While these proteins can found in breast cancer cells, further work is required to uncover their exact roles. [DRAM-4 and DRAM-5 are compensatory regulators of autophagy and cell survival in nutrient-deprived conditions in The FEBS Journal]

 

New CRUK Scotland Centre announced

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.

The joint Centre will have six tumour-specific research themes, based on cancer types that profoundly affect the Scottish population (bowel, liver and pancreas cancer, and mesothelioma) or in which there is a growing expertise in Scotland (brain and women's cancer). Underpinning this work will be state-of-the-art infrastructure, particularly in model systems, pathology and advanced imaging, that will ensure a translational pipeline from basic science to the clinic remains open and available to all.

Crucially, the Centre will also make best use of the Scottish clinical 'cancer environment' and data – both its provision and analysis – will be central to enabling the Centre to link real-world cancer patients and their information to research into the biology of disease progression and response, focused prevention and early detection initiatives, experimental medicine projects and preclinical studies.

Together, by maximising the value of its clinical and scientific resources, the CRUK Scotland Centre will benefit Scottish patients and CRUK's mission to prevent cancer and improve 10-year survival rates to 75% by 2034.

Follow link to CRUK website for more details: https://news.cancerresearchuk.org/2022/01/24/seven-centres-to-form-new-cancer-research-uk-network/

Inspiring women: Editors in the spotlight

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

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