Hydrogen-Deuterium Exchange Dynamics of NISTmAb Measured by Small Angle Neutron Scattering.

Understanding protein dynamics and conformational stability holds great significance in biopharmaceutical research. Hydrogen-deuterium exchange (HDX) is a quantitative methodology used to examine these fundamental properties of proteins. HDX involves measuring the exchange of solvent-accessible hydrogens with deuterium, which yields valuable insights into conformational fluctuations and conformational stability. While mass spectrometry is commonly used to measure HDX on the peptide level, we explore a different approach using small-angle neutron scattering (SANS). In this work, SANS is demonstrated as a complementary and noninvasive HDX method (HDX-SANS). By assessing subtle changes in the tertiary and quaternary structure during the exchange process in deuterated buffer, along with the influence of added electrolytes on protein stability, SANS is validated as a complementary HDX technique. The HDX of a model therapeutic antibody, NISTmAb, an IgG1κ, is monitored by HDX-SANS over many hours using several different formulations, including salts from the Hofmeister series of anions, such as sodium perchlorate, sodium thiocyanate, and sodium sulfate. The impact of these formulation conditions on the thermal stability of NISTmAb is probed by differential scanning calorimetry. The more destabilizing salts led to heightened conformational dynamics in mAb solutions even at temperatures significantly below the denaturation point. HDX-SANS is demonstrated as a sensitive and noninvasive technique for quantifying HDX kinetics directly in mAb solution, providing novel information about mAb conformational fluctuations. Therefore, HDX-SANS holds promise as a potential tool for assessing protein stability in formulation.

Micelle Formation and Phase Separation of Poloxamer 188 and Preservative Molecules in Aqueous Solutions Studied by Small Angle X-ray Scattering.

Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can induce aggregation and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution. A systematic study is conducted here to understand the phase behavior and morphological causes of aggregation of P188 in the presence of the preservatives phenol and benzyl alcohol, primarily using small-angle x-ray scattering (SAXS). Based on SAXS results, P188 remains as unimers in solution when below a certain phenol concentration. Upon increasing the phenol concentration, a regime of micelle formation is observed due to the interaction between P188 and phenol. Further increasing the phenol concentration causes mixtures to become turbid and phase-separate over time. The effect of benzyl alcohol on the phase behavior is also investigated.

Ireland's Higher Education Teachers Have a National Professional Development Framework, Now What?

Momentum has been building for professional development (PD) for all staff who teach in Irish higher education - they now have the national Professional Development Framework (PDF) to support them in planning and engaging with authentic, inclusive, scholarly, learner-centred and collaborative PD across their career. In mid-2016, the PD Framework was published by the National Forum for the Enhancement of Teaching and Learning. In 2017, the PDF was piloted with 215 individuals from 22 professional identity groups from across the sector, working with the framework to reflect on their professional practice and set goals for their future professional development. This initial implementation phase has now been fully evaluated and a robust evidence-base of 'what works, and why' in relation to staff engagement with the PDF is in place. Disseminating findings and continuing to engage with the sector through relevant platforms such as HEIT is key to advancing this work. Early 2018 witnessed the HEA publishing the HE System Performance Framework 2018-2020 with two recommendations which are key to the momentum of the PDF: • Implementation of the Continuous Professional Development Framework • Number of staff with "Digital Badges" for completed CPD by academic year Given these significant developments over a relatively short period, we are now asking the sector, what needs to happen next for the PDF to continue to drive progress for individual's careers and support them in dealing with change and transformation in their professional practice?