Mainstreaming climate change education in UK higher education institutions

Key messages: • Mainstreaming Climate Change Education (CCE) across all learning and operational activities enables Higher Education Institutions (HEIs) to better serve their core purpose of preparing learners for their roles in work and wider society, now and in the future. • Student and employer demand for climate change education is growing, not just in specialist subjects but across all degree pathways. • The attitudes, mindsets, values and behaviours that graduates need to engage with climate change include the ability to deal with complexity, work collaboratively across sectors and disciplines and address challenging ethical questions. • The complexity of the climate crisis means all disciplines have a role to play in delivering education for the net-zero transition. Embedding interdisciplinarity is crucial to ensuring that our response to climate change makes use of all of the expertise HEIs have to offer and promotes knowledge exchange and integration for students and staff. • Student-centered CCE, including peer-to-peer learning, is a powerful tool for facilitating an inclusive and empowering learning experience, and developing graduates as change agents for the climate and ecological crisis. • HEIs should develop learning outcomes for CCE that include understanding the scale, urgency, causes, consequences and solutions of climate change; how social norms and practices are driving the climate crisis; and the ability to identify routes to direct involvement in solutions via every discipline. • Pedagogical approaches to teaching CCE should enable learners to engage with, and respond to, climate change as a “real-world” problem, such as through experiential learning. • Further recommendations for the HEI sector include developing a strategy for aligning CCE teaching provision with governance structures; partnering with industry, government and third sector organisations to enable context-specific CCE; and working with trade unions and accreditation bodies to enable curriculum reform

Mainstreaming Climate Change Education in UK Higher Education Institutions

Key messages• Mainstreaming Climate Change Education (CCE) across all learning and operational activities enables Higher Education Institutions (HEIs) to better serve their core purpose of preparing learners for their roles in work and wider society, now and in the future.• Student and employer demand for climate change education is growing, not just in specialist subjects but across all degree pathways.• The attitudes, mindsets, values and behaviours that graduates need to engage with climate change include the ability to deal with complexity, work collaboratively across sectors and disciplines and address challenging ethical questions.• The complexity of the climate crisis means all disciplines have a role to play in delivering education for the net-zero transition. Embedding interdisciplinarity is crucial to ensuring that our response to climate change makes use of all of the expertise HEIs have to offer and promotes knowledge exchange and integration for students and staff.• Student-centered CCE, including peer-to-peer learning, is a powerful tool for facilitating an inclusive and empowering learning experience, and developing graduates as change agents for the climate and ecological crisis.• HEIs should develop learning outcomes for CCE that include understanding the scale, urgency, causes, consequences and solutions of climate change; how social norms and practices are driving the climate crisis; and the ability to identify routes to direct involvement in solutions via every discipline.• Pedagogical approaches to teaching CCE should enable learners to engage with, and respond to, climate change as a “real-world” problem, such as through experiential learning.• Further recommendations for the HEI sector include developing a strategy for aligning CCE teaching provision with governance structures; partnering with industry, government and third sector organisations to enable context-specific CCE; and working with trade unions and accreditation bodies to enable curriculum reform

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

TRRAP is essential for regulating the accumulation of mutant and wild-type p53 in lymphoma

Tumors accumulate high levels of mutant p53 (mutp53), which contributes to mutp53 gain-of-function (GOF) properties. The mechanisms that underlie such excessive accumulation are not fully understood. To discover regulators of mutp53 protein accumulation, we performed a large-scale RNA interference (RNAi) screen in a Burkitt's lymphoma (BL) cell line model. We identified TRRAP, a constituent of several histone acetyltransferase (HAT) complexes, as a critical positive regulator of both mutp53 and wild-type p53 (wtp53) levels. TRRAP silencing attenuated p53 accumulation in lymphoma and colon cancer models, while TRRAP overexpression increased mutp53 levels, suggesting a role for TRRAP across cancer entities and p53 mutations. Through CRISPR-Cas9 screening, we identified a 109 amino acid region in the N-terminal HEAT repeat region of TRRAP which was crucial for mutp53 stabilization and cell proliferation. Mass spectrometric analysis of the mutp53 interactome indicated that TRRAP silencing caused degradation of mutp53 via the MDM2-proteasome axis. This suggests that TRRAP is vital for maintaining mutp53 levels by shielding it against the natural p53 degradation machinery. To identify drugs that alleviated p53 accumulation similarly to TRRAP silencing, we performed a small molecule drug screen and found that inhibition of histone deacetylases (HDACs), specifically HDACs1/2/3, decreased p53 levels to a comparable extent. In summary, here we identify TRRAP as a key regulator of p53 levels and link acetylation-modifying complexes to p53 protein stability. Our findings may provide clues for therapeutic targeting of mutp53 in lymphoma and other cancers