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- Kennedy, S. A., et al.
(författare)
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Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
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- Cable, Jennifer, et al.
(författare)
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Progress in vaccine development for infectious diseases : a Keystone Symposia report
- 2023
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Ingår i: Annals of the New York Academy of Sciences. - : John Wiley & Sons. - 0077-8923 .- 1749-6632. ; 1524:1, s. 65-86
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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- Walton, Courtney C, et al.
(författare)
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Psychological Safety for Mental Health in Elite Sport : A Theoretically Informed Model.
- 2024
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Ingår i: Sports Medicine. - : Springer. - 0112-1642 .- 1179-2035. ; 54:3, s. 557-564
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Tidskriftsartikel (refereegranskat)abstract
- Elite sports contexts are highly pressurised and frequently enforce a win-at-all-costs approach. This narrow focus on performance outcomes can potentially contribute in negative ways to the mental health of those within these environments. In this Current Opinion paper, we propose a model that outlines how key elements contributing to psychologically safe or unsafe environments may contribute to better or worse mental health outcomes, respectively. In an environment in which individuals feel safe to show their authentic selves rather than 'wear a mask', different experiences of mental health are likely to be normalised, help-seeking behaviour increased, and thus, mental health outcomes enhanced. We outline how sports teams and organisations can contribute to this through the creation of appropriate policies and procedures, in addition to leaders modelling and reinforcing positive cultural norms. It is intended that the theoretical model can inform stakeholders in elite sport as well as future research directions.
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