IUBMB Trainee Initiative: supporting emerging biochemists and molecular biologists around the world.

The International Union of Biochemistry and Molecular Biology (IUBMB) Trainee Initiative aims to identify challenges experienced by biochemistry and molecular biology trainees and create programming to foster their growth and development as the next generation of scientists. Here, we highlight resources and events developed by the Trainee Initiative in their endeavor to support trainees around the world.

Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.

MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs), which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs. In crystal structures, the six immunoglobulin (Ig) and single fibronectin III domains of MDGA1 reveal a striking compact, triangular shape, both alone and in complex with NLGNs. Whether this unusual domain arrangement is required for biological function or other arrangements occur with different functional outcomes is unknown. Here, we show that WT MDGA1 can adopt both compact and extended 3D conformations that bind NLGN2. Designer mutants targeting strategic molecular elbows in MDGA1 alter the distribution of 3D conformations while leaving the binding affinity between soluble ectodomains of MDGA1 and NLGN2 intact. In contrast, in a cellular context, these mutants result in unique combinations of functional consequences, including altered binding to NLGN2, decreased capacity to conceal NLGN2 from NRXN1ß, and/or suppressed NLGN2-mediated inhibitory presynaptic differentiation, despite the mutations being located far from the MDGA1-NLGN2 interaction site. Thus, the 3D conformation of the entire MDGA1 ectodomain appears critical for its function, and its NLGN-binding site on Ig1-Ig2 is not independent of the rest of the molecule. As a result, global 3D conformational changes to the MDGA1 ectodomain via strategic elbows may form a molecular mechanism to regulate MDGA1 action within the synaptic cleft.

Reducing plastic waste in scientific protocols by 65% - practical steps for sustainable research.

Although scientists are generally motivated to adopt sustainable practices in their research, a lack of education is often limiting. Here, I aim to fill this gap by illustrating how to substantially reduce single-use plastic waste in scientific protocols. This article will outline the translation of the three fundamental principles of reduction, reuse, and miniaturization into experimental practice. The transfection of neurons in sterile conditions will be provided as a concrete example to discuss opportunities for change. Simply by reducing, miniaturizing, and reusing, a decrease in plastic waste of approximately 65% was achieved for exchangeable items. This article demonstrates the feasibility of adopting sustainable practices without compromising workflows or data quality.

A new approach to making scientific research more efficient - rethinking sustainability.

As interest in sustainability grows, many researchers raise questions about changing scientific practices. To enable effective change, we reconceptualize sustainability as an approach that optimizes the efficiency of procedures, thereby benefiting scientists and minimizing environmental footprints. Since the implementation of sustainable approaches can be challenging, we describe the 6R concept as a framework to arrive at actionable steps.