Development of a strategy for the expansion of online teaching at the University of Würzburg based on the experiences of lecturers and students in the pandemic years 2020/21.

Background: Owing to the COVID-19 pandemic, the summer of 2020 saw face-to-face teaching replaced by online teaching. The question arose as to how digitalisation may be implemented meaningfully. The views of lecturers and students on past online programmes were gathered in order to identify potential and future prospects. Project description: An exploratory, guidelines-based interview study was conducted during the clinical phase of the medicine degree at the Faculty of Medicine in Würzburg. Five lecturers and five students were interviewed in the winter semester of 2020/21. This was followed by a content analysis evaluation according to Kuckartz, with the help of MAXQDA. Results: Online teaching offers more flexibility and security for the future. Hybrid formats (e.g., blended learning) are in demand. While theoretical knowledge can be taught online, face-to-face teaching remains essential in practical training. Digital elements must be developed didactically and anchored in the curriculum. Interaction and direct feedback between students and lecturers are key aspects of this. Discussion: Online teaching in medicine offers numerous potentials and didactic design options that can improve the degree programme in a competency-based manner. Combined teaching formats are particularly effective in this regard. Fittingly conceived, multimedia teaching formats enable students to approach their studies in a focused manner. The points raised during the interviews correspond with the fundamental principles of the ARCS model, which was developed to strengthen continuous motivation in students. Conclusion: Well-thought-out design and integration of online teaching can contribute to attractive, efficient, and future-oriented teaching/learning activities. Decisive factors are the collaboration of everyone involved and adequate provision of both time and financial resources.

A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination.

In meiosis, crossover (CO) formation between homologous chromosomes is essential for faithful segregation. However, misplaced meiotic recombination can have catastrophic consequences on genome stability. Within pericentromeres, COs are associated with meiotic chromosome missegregation. In organisms ranging from yeast to humans, pericentromeric COs are repressed. We previously identified a role for the kinetochore-associated Ctf19 complex (Ctf19c) in pericentromeric CO suppression. Here, we develop a dCas9/CRISPR-based system that allows ectopic targeting of Ctf19c-subunits. Using this approach, we query sufficiency in meiotic CO suppression, and identify Ctf19 as a mediator of kinetochore-associated CO control. The effect of Ctf19 is encoded in its NH2-terminal tail, and depends on residues important for the recruitment of the Scc2-Scc4 cohesin regulator. This work provides insight into kinetochore-derived control of meiotic recombination. We establish an experimental platform to investigate and manipulate meiotic CO control. This platform can easily be adapted in order to investigate other aspects of chromosome biology.

Kinetochores, cohesin, and DNA breaks: Controlling meiotic recombination within pericentromeres.

In meiosis, DNA break formation and repair are essential for the formation of crossovers between homologous chromosomes. Without crossover formation, faithful meiotic chromosome segregation and sexual reproduction cannot occur. Crossover formation is initiated by the programmed, meiosis-specific introduction of numerous DNA double-strand breaks, after which specific repair pathways promote recombination between homologous chromosomes. Despite its crucial nature, meiotic recombination is fraud with danger: When positioned or repaired inappropriately, DNA breaks can have catastrophic consequences on genome stability of the resulting gametes. As such, DNA break formation and repair needs to be carefully controlled. Within centromeres and surrounding regions (i.e., pericentromeres), meiotic crossover recombination is repressed in organisms ranging from yeast to humans, and a failure to do so is implicated in chromosome missegregation and developmental aneuploidy. (Peri)centromere sequence identity and organization diverge considerably across eukaryotes, yet suppression of meiotic DNA break formation and repair appear universal. Here, we discuss emerging work that has used budding and fission yeast systems to study the mechanisms underlying pericentromeric suppression of DNA break formation and repair. We particularly highlight a role for the kinetochore, a universally conserved, centromere-associated structure essential for chromosome segregation, in suppressing (peri)centromeric DNA break formation and repair. We discuss the current understanding of kinetochore-associated and chromosomal factors involved in this regulation and suggest future avenues of research.

The kinetochore prevents centromere-proximal crossover recombination during meiosis.

During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes.