Leading as designing: how educational developers in leadership and management studies can use architectural design to facilitate student learning about delivering innovation

This paper describes a qualitative observational study of how a work based learning masters leadership development programme for middle managers in health and social care in the UK introduced students to key aspects of delivering innovation, through a formative assignment on contemporary architectural design. Action learning and activity theoretical approaches were used to enable students to explore common principles of leading the delivery of innovation. Between 2001 and 2013 a total of 89 students in 7 cohorts completed the assignment. Evaluation lent support for the view that the assignment provided a powerful learning experience for many. Several students found the creativity, determination and dedication of architects, designers and structural engineers inspirational in their ability to translate a creative idea into a completed artefact, deploy resources and negotiate complex demands of stakeholders. Others expressed varying levels of self-empowerment as regards their capacity for fostering an equivalent creativity in self and others. Theoretical approaches in addition to activity theory, including Engeström’s concepts of stabilisation knowledge and possibility knowledge, are discussed to explain these differing outcomes and to clarify the challenges and opportunities for educational developers seeking to utilise cross-disciplinary, creative approaches in curriculum design.

Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells.