The ␣-crystallins are members of the small heat shock protein family of molecular chaperones that have evolved to minimize intracellular protein aggregation; however, they are also implicated in a number of protein deposition diseases. In this study, we employed novel mass spectrometry techniques to investigate the changes in quaternary structure associated with this switch from chaperone to adjuvant of aggregation. We replicated the oligomeric rearrangements observed for post-translationally modified ␣-crystallins, without altering the protein sequence, by refolding the ␣-crystallins in vitro. This refolding resulted in a loss of dimeric substructure concomitant with an augmentation of substrate affinity. We show that packaging of small heat shock proteins into dimeric units is used to control the level of chaperone function by regulating the exposure of hydrophobic surfaces. We propose that a bias toward monomeric substructure is responsible for the aberrant chaperone behavior associated with the ␣-crystallins in protein deposition diseases.The small heat shock proteins (sHSPs) 4 ␣A-and ␣B-crystallin are most prevalent in the vertebrate eye lens, where they are found co-assembled and maintain lens transparency by preventing other proteins from forming light-scattering aggregates (1), but are also found in other tissues (2). It is clear that these proteins have the ability to sequester substrates that have become partially unfolded under conditions of stress to preserve them in a state competent for refolding (3-6). However, molecular mechanisms of their function and regulation remain incompletely understood, particularly regarding aberrant behavior in the transitions that occur to bring about disease states (7).Structurally, the sHSPs are characterized by their low monomeric molecular mass, their assembly into oligomers, and the presence of a well conserved "␣-crystallin" domain (3-6). Although crystal structures exist for some of the monodisperse members of the family (3), the extreme polydispersity of many of the mammalian sHSPs, including the ␣-crystallins, has hampered crystallographic analysis (4). Common to the sHSPs for which high resolution structures have been published is the existence of dimers as "building blocks" of the larger oligomer (3, 6). We have reported that recombinant ␣A and ␣B form a range of oligomers with a notable preference for an even number of subunits (9, 10). This suggests that dimeric substructure is a key characteristic of the sHSPs, and indeed, dimers have been proposed as the active "chaperoning unit" of the sHSPs (6). In our previous study on ␣B isolated from the lens under denaturing conditions, we observed a difference in the proportion of oligomers containing an even or odd number of subunits (11). This observation, along with recent work showing structural changes in the ␣-crystallins upon renaturation from urea (12), suggests that in vitro refolding provides a means of modulating the quaternary structure of these proteins. Here, we exploit this phenomenon to examine the...

Double degrees (also called joint or combined degrees) -programs of study combining two bachelor degrees -are increasingly popular in Australian universities, particularly among women. A case study using qualitative and quantitative surveys of current and past double degree students is presented. The study indicates that double degrees benefit students in providing a broad education and increasing skills and options. However, benefits are not fully realised because of administrative difficulties, lack of support and absence of 'learning communities'. These problems arise because double degrees sit outside the disciplinary structure of universities. As such, however, double degrees have potential to provide transdisciplinary education. We suggest initiatives that would improve the experience, performance and persistence of double degrees students. They would also build the skills of integration, boundary work, communication and teamwork associated with transdisciplinarity. These skills not only equip students for a range of employment; they are sorely needed in society. AbstractDouble degrees (also called joint or combined degrees) -programs of study combining two bachelor degrees -are increasingly popular in Australian universities, particularly among women. A case study using qualitative and quantitative surveys of current and past double degree students is presented. The study indicates that double degrees benefit students in providing a broad education and increasing skills and options. However, benefits are not fully realised because of administrative difficulties, lack of support and absence of 'learning communities'. These problems arise because double degrees sit outside the disciplinary structure of universities. As such, however, double degrees have potential to provide transdisciplinary education. We suggest initiatives that would improve the experience, performance and persistence of double degrees students. They would also build the skills of integration, boundary work, communication and teamwork associated with transdisciplinarity. These skills not only equip students for a range of employment; they are sorely needed in society.