Dear All,

In this issue we welcome two new appointments to the School, Dr Chris Hall and Dr Nikki Moreland. The dual appointment of Chris and Nikki reflects our desire to strengthen teaching and research in the area of immunology that has been eroded by the retirements of senior academic staff in the School.

Over the next two years in the lead up to the next PBRF exercise, we have a number of staff who have indicated their intentions to retire. While these colleagues will be sorely missed, the retirement of this group of senior staff offers a unique opportunity to reshape the research directions of the School and I will be seeking your input on this process.

It also throws up a number of challenges, as many of the retiring staff have provided outstanding academic service and leadership to the school, their respective departments and their scientific disciplines over the course their careers. 

Hence we need to start thinking now about succession planning to develop the next generation of academic leaders within the school.

In this regard, our implementation of the shift of the governance of the post graduate programme in Biomedical Science to the school offers an excellent opportunity for younger staff to take on significant service roles that will allow them to demonstrate the leadership required to shape the future direction of teaching and research in the Biomedical Sciences.

As discussed at the school forum we will need to appoint a new Board of Studies, a director of the Honours programme, course directors for new compulsory courses, and conduct a review of our existing 700 level offerings. 

Things are changing and in change there is opportunity. I hope you all are prepared to embrace these changes and are prepared to play your part in ensuring they are successfully implemented.

Regards,

Professor Paul Donaldson
Head of School, School of Medical Sciences
Faculty of Medical and Health Sciences

High Impact papers

Fang Yan, Johnson J Liu, Virginia Ip, Stephen M F Jamieson, Mark J McKeage had published a paper ‘Role of platinum DNA damage-induced transcriptional inhibition in chemotherapy-induced neuronal atrophy and peripheral neurotoxicity’ in December 2015.

Findings point to a new stepwise mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum-DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy.

Dorsal root ganglion neurons may be particularly vulnerable to this neurotoxicity due to their high global transcriptional outputs, demonstrated in this study by click chemistry quantitative fluorescence imaging.

Read the paper

 Lynnette R Ferguson, was involved in a genetic association study on inherited determinants of Crohn's disease and ulcerative colitis phenotypes.

Crohn’s disease and ulcerative colitis have been considered as the two major forms of inflammatory bowel disease. Treatmentstrategies have historically been determined by this binary categorisation.

Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn’s disease and ulcerative colitis.

The findings of the largest phenotype–genotype study in IBD to date were reported in The Lancet earlier this year. The study analysed genetic data and associated this with disease behaviour from nearly 30,000 patients with IBD, from 49 centres (including the University of Auckland) across 16 different countries in Europe, North America and Australasia.

The data revealed that there should be three distinct disease groups within IBD —ileal Crohn's disease, colonic Crohn's disease and ulcerative colitis—instead of the current classification into two groups.

This important study has significant implications for the determination of optimal treatment and maintenance of remission.

Read the paper

Tsai, C., Loh, JMS and Proft, T have recently published an article entitled ‘Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing’.

It is a comprehensive review article on the use of wax moth larvae (Galleria mellonella) as bacterial infection models. This was published online by ‘Virulence’, a well-known infectious disease journal with an IF of 4.22. The printed version will be available soon.

Read the paper

The Molecular Modelling laboratory at the Auckland Cancer Society Research Centre

The molecular modelling laboratory in the Auckland Cancer Society Research Centre (ACSRC) builds on a rich history in structure guided drug design.

The earliest application in the ACSRC used hand-built ball-and-stick models of DNA to look at DNA intercalating drugs in action. Computer based methods eventually took over and have allowed researchers to simulate the interactions for a much wider range of targets ensuring that molecular modelling occupies a leading role in most of the early stage drug design projects at the ACSRC.

Some of the applications covered by molecular-modelling include prediction of protein ligand interactions, calculating protein motion, and chem-informatics.

One of the laboratory’s main interests is in the use of protein structure to discover new chemical matter that will modulate protein function. In this they also collaborate with others who wish to discover new molecules to study their systems of interest.

The methods they use can be classed as either receptor or ligand based. Receptor based methods use information from the target structure, while the ligand based ones use information from ligands active at the target. Molecular docking is a receptor based method, and the method used most often in the laboratory.

Here, small organic molecules are modelled in a specific site on the protein, an enzyme active site perhaps, and evaluated for shape and chemical complementarity. Digital libraries of millions of compounds are maintained for this purpose. They curate these according to the current understanding of drug-like and lead-like properties and the growing knowledge around “frequent hitters” (promiscuous compounds that show up in many screens).

They apply both receptor and ligand based methods in large scale virtual screening campaigns – the computer based version of high through put screening, whereas molecular docking is their major tool in small scale structure guided analogue design. All of their large scale screens use the high performance computing infrastructure provided by the National eScience Infrastructure and the University of Auckland Centre for eResearch.

Some of the targets they have investigated include lipid and protein kinases, reductases and GPCRs where ligand binding sites are often well defined pockets. They also have some interesting cases where the pocket is less well defined, including hormone binding sites on cell surface receptors and carbohydrate binding proteins.

A new area of interest for them is in the physical response of lipid kinases to drug binding and how this affects the interface between the protein and a lipid bilayer.

A big welcome to Vickie Haake who has recently been appointed to the position of Group Services Team Leader.

Vickie will manage and support the Group Services Coordinators who currently provide support to academic heads.

She will also continue to lead and coordinate Human Resources and Recruitment Processes and procedures within the School of Medical Sciences and School of Pharmacy.

Great to have you on board Vickie.