Development of key practical skills is fundamental to bioscience courses in higher education. With limitations on access to laboratory time due to the COVID-19 pandemic, a “Bioskills at home” kit was developed to create opportunities for first year undergraduate students to develop these skills using online support resources to guide their activities and build communities of learning. Equipment and activities in this kit enabled students to practice key skills such as pipetting, data handling, experimental design and microscopy, as well as build an online peer learning community through the use of discussion boards and microscopy competitions that encouraged students to explore their local environment. Students who engaged with these activities reported increased confidence in key practical skills. Practical assessment of skills showed that that there was no reduction in the proportion of students who succeeded in achieving the pipetting learning objective compared to previous years, despite a significantly reduced on-campus provision. Although the celebration event to choose the microscopy competition winners was well attended, there was limited use of the discussion boards by students to build a community of learning during the term. Refinement of this initiative will focus on providing greater scaffolding to encourage greater engagement with activities and enhance community building.
The Caf1/CNOT7 nuclease is a catalytic component of the Ccr4-Not deadenylase complex, which is a key regulator of post-transcriptional gene regulation. In addition to providing catalytic activity, Caf1/CNOT7 and its paralogue Caf1/CNOT8 also contribute a structural function by mediating interactions between the large, non-catalytic subunit CNOT1, which forms the backbone of the Ccr4-Not complex and the second nuclease subunit Ccr4 (CNOT6/CNOT6L). To facilitate investigations into the role of Caf1/CNOT7 in gene regulation, we aimed to discover and develop non-nucleoside inhibitors of the enzyme. Here, we disclose that the tri-substituted 2-pyridone compound 5-(5-bromo-2-hydroxy-benzoyl)-1-(4-chloro-2-methoxy-5-methyl-phenyl)-2-oxo-pyridine-3-carbonitrile is an inhibitor of the Caf1/CNOT7 nuclease. Using a fluorescence-based nuclease assay, the activity of 16 structural analogues was determined, which predominantly explored substituents on the 1-phenyl group. While no compound with higher potency was identified among this set of structural analogues, the lowest potency was observed with the analogue lacking substituents on the 1-phenyl group. This indicates that substituents on the 1-phenyl group contribute significantly to binding. To identify possible binding modes of the inhibitors, molecular docking was carried out. This analysis suggested that the binding modes of the five most potent inhibitors may display similar conformations upon binding active site residues. Possible interactions include π-π interactions with His225, hydrogen bonding with the backbone of Phe43 and Van der Waals interactions with His225, Leu209, Leu112 and Leu115.
The human Ccr4–Not complex is a central regulator of post-transcriptional gene regulation, impacting on translation and mRNA degradation. In mRNA degradation, Ccr4–Not participates in the shortening of the mRNA poly(A)-tail via two catalytic subunits. The Caf1 nuclease is encoded by the highly similar paralogues CNOT7 or CNOT8. In addition to its poly(A)-specific ribonuclease activity, this subunit also provides a structural role by binding Ccr4, the second catalytic nuclease subunit encoded by the paralogues CNOT6 or CNOT6L. To facilitate investigations into the roles of the Caf1 subunit, and to complement genetic tools, we set out to identify inhibitors of the enzymatic activity of Caf1/CNOT7. To this end, we screened a library of 10,880 chemically diverse, drug-like compounds using a fluorescence-based biochemical assay. This effort led to the discovery of 15 inhibitors of Caf1/CNOT7 with biochemical IC50 values below 25 μM. Molecular docking was performed to explore potential binding modes of these compounds. The compounds reported here may be useful to differentiate between catalytic and non-catalytic roles of Caf1/CNOT7. In addition, they may be valuable starting points for the development of more potent inhibitors of the Caf1/CNOT7 poly(A)-selective ribonuclease.
Practical laboratory training is a key component of biosciences education, essential for developing critical skills and bridging the gap between theory and practice. The ‘Bioskills at home kit’, originally developed during the COVID-19 pandemic, was created to support first-year students in developing core laboratory skills at a time when access to in-person sessions was limited. Each kit contained equipment and guided activities focused on pipetting, microscopy, experimental design and microbial growth curve analysis. This study aimed to assess the educational impact of this kit using a mixed-methods approach. Data were collected across three student cohorts (2020/21, 2021/22 and 2024/25) using surveys and a focus group and analysed using appropriate statistical analyses and reflexive thematic analysis, respectively. The study evaluated the impact of the Bioskills at home kit on student learning across the cognitive, affective and psychomotor domains. Aspects of student experience, including perceived benefits, barriers to engagement and suggestions for improvement, were investigated, and student attainment from a compulsory laboratory assessment spanning seven academic years (2018/19–2024/25) was analysed. Results show that students experienced improved understanding of theoretical concepts, confidence, enjoyment and enhanced technical skills. Student attainment in practical assessment was also improved. Embedding the delivery of the kit in a more structured way within the personal tutorial system in subsequent years improved student engagement which was a challenge during the first year of intervention. Here, we demonstrate the successful implementation of the Bioskills at home kit which offers a scalable and inclusive model for flexible laboratory teaching.
Practical laboratory training is a key component of Biosciences education, essential for developing critical skills and bridging the gap between theory and practice. The ‘Bioskills at home kit’, originally developed during the COVID-19 pandemic, was created to support first-year students in developing core laboratory skills at a time when access to in-person sessions was limited. Each kit contained equipment and guided activities focused on pipetting, microscopy, experimental design and microbial growth curve analysis. This study aimed to access the educational impact of the kit using a mixed-methods approach. Data were collected across three student cohorts (2020/21, 2021/22 and 2024/25) using surveys and a focus group and were analysed using descriptive statistics and reflexive thematic analysis, respectively. The study evaluated the impact of the Bioskills at home kit on student learning across the cognitive, affective and psychomotor domains. Student experience including perceived benefits, barriers to engagement and suggestions for improvement were investigated and student attainment from a compulsory laboratory assessment spanning seven academic years (2018/19 – 2024/25) were analysed. Results show that students experienced improved understanding of theoretical concepts, increased confidence, enjoyment and enhanced technical skills. Student attainment in practical assessment was also improved. Embedding the delivery of the Bioskills at home kit in a more structured way within the personal tutorial system in subsequent years significantly improved student engagement which was a challenge during the first year of intervention. We demonstrate the successful implementation of the Bioskills at home kit, offering a scalable and inclusive model for flexible laboratory teaching.
Practical laboratory training is a key component of Biosciences education, essential for developing critical skills and bridging the gap between theory and practice. The ‘Bioskills at home kit’, originally developed during the COVID-19 pandemic, was created to support first-year students in developing core laboratory skills at a time when access to in-person sessions was limited. Each kit contained equipment and guided activities focused on pipetting, microscopy, experimental design and microbial growth curve analysis. This study aimed to assess the educational impact of this kit using a mixed-methods approach. Data were collected across three student cohorts (2020/21, 2021/22 and 2024/25) using surveys and a focus group and analysed using appropriate statistical analyses and reflexive thematic analysis, respectively. The study evaluated the impact of the Bioskills at home kit on student learning across the cognitive, affective and psychomotor domains. Aspects of student experience including perceived benefits, barriers to engagement and suggestions for improvement were investigated and student attainment from a compulsory laboratory assessment spanning seven academic years (2018/19 – 2024/25) were analysed. Results show that students experienced improved understanding of theoretical concepts, confidence, enjoyment and enhanced technical skills. Student attainment in practical assessment was also improved. Embedding the delivery of the kit in a more structured way within the personal tutorial system in subsequent years improved student engagement which was a challenge during the first year of intervention. Here, we demonstrate the successful implementation of the Bioskills at home kit which offers a scalable and inclusive model for flexible laboratory teaching.