Jessica Petri in the Cook Lab

10 June 2013

Jessica Petri has just started her PhD in Professor Greg Cook’s lab. Jessica completed her BSc (BSc(Hons) equivalent) at the Goethe University in Frankfurt am Main, in her home country Germany. Her Bachelor thesis was titled “Deletion and overexpression from putative translation regulators in Haloferax volcanii”. She came to Dunedin in December 2012 to work on a Dean’s Prestigious Summer Scholarship project in the Cook lab. During Jessica’s summer studentship, she worked with an enzyme (ATP synthase) used by methanogens (methane producing microorganisms) to generate energy. Jessica is enjoying life in New Zealand.

The overall goal of the Cook lab’s research is to understand at a cellular and molecular level how microorganisms adapt to different environments. One of the main aims is the development of drugs to target metabolic enzymes to control the growth of methanogens, methane-producing microorganisms. This research has the potentially very practical aim of reducing greenhouse gas (methane) emissions in ruminant animals. The New Zealand government is very supportive of this research as New Zealand surprisingly produces almost the same amount of greenhouse gasses per capita as the United States. In order to comply with the Kyoto protocol, New Zealand’s greenhouse gas emissions need to be brought down to the level of 1990. Unlike in most other developed countries, most of New Zealand’s emissions originate from agriculture. This novel research aims to tailor make designer drugs for environmental problems like greenhouse gas-producing bacteria, rather than using drugs that were developed for humans, as is currently done in many agricultural sectors. There is a need to find an effective inhibitor of methanogen metabolism. This will be sought by high throughput screenings of compound libraries against the methanogen ATP synthase and growth. Jessica’s PhD research will focus on a structural analysis of the methanogen ATP synthase to understand regulation and enable rational design of inhibitors. Interestingly, some methanogens have been implicated in human obesity, which opens up exciting prospects for future research.

We wish Jessica and her colleagues in the Cook lab all the best with their groundbreaking research.

Harnessing the power of natural killer cells

7 June 2013

A/P Alex McLellan (Microbiology & Immunology) was recently awarded $15,528 from the Dean's Bequest Funds for a project on harnessing the power of natural killer cells to boost anti-tumour immune responses.

The immune system plays an important role in conventional cancer therapy following radiation or chemotherapy for cancers. Newly emerging methods for 'immunotherapy' offers an additional ways to further boost anti-cancer treatment by further stimulating the immune system to attack tumours. A/P McLellan's laboratory has shown that certain types of commensal bacteria act as adjuvants to increase the response of the immune system to tumours. These adjuvants act on white blood cells termed dendritic cells (DC) and stimulate a potent anti-tumour response. They have recently discovered that innate lymphocytes natural killer cells (NK cells) are essential for the efficiency of these bacterial adjuvants. The novel aspect of dendritic cell stimulation of NK cells indicates important links between the innate (NK cells) and the adaptive immune response (DC). This OSMS school award will enable the completion of this work for peer-reviewed publication in a widely read and high ranking international journal and will encourage further clinical investigation into new methods for immunotherapy of cancer.

An investigation into the molecular mechanisms underlying epilepsy and autism

31 May 2013

Dr Beulah Leitch (Anatomy) was recently awarded $17,300 from the Dean's Bequests to investigate the molecular mechanisms underlying the comorbid neurodevelopmental disorders, epilepsy and autism.

Epilepsy and autism spectrum disorder (ASD) are highly comorbid; that is they can occur simultaneously in the same person. Current estimates of co-diagnoses in children with epilepsy and ASD stand at approximately 20–25%. However, this estimate rises to nearly 40% within the ASD population. Autism is an increasingly recognized, heritable behavioral disorder. Children diagnosed with genetic forms of epilepsy and ASD share overlapping clinical symptoms, which suggests a common dysfunction in central nervous system development leads to the onset of these interrelated disorders.  Available research data in ASD suggests that the deficits in social cognition and related neurocognitive functions, which typify ASD, are linked to disorders in neural connectivity leading to glutamate signalling defects and imbalances in excitatory and inhibitory neuronal circuits. Recent evidence suggests a link between autism and dysfunction in the cerebellum due to altered glutamatergic synaptic proteins. For example, abnormally increased levels of proteins associated with excitatory glutamatergic synapses have been found in post-mortem cerebella from autistic patients.

This project proposes to investigate cellular and molecular changes at cerebellar synapses in a mouse model which presents with altered glutamatergic signaling due a deficit in a trafficking protein for AMPA-type glutamate receptors resulting in absence epilepsy and cerebellar dysfunctional traits characteristics of autism. The overarching aim is to understand how disruptions to excitatory neurotransmission at the level of glutamate receptor–synaptic protein interactions may contribute to synaptic dysfunction and to unravel the roles these proteins play in the comorbid disorders of childhood epilepsy and autism. This study will provide pilot data for a targeted study to identify cell specific and synapse specific changes in postmortem autistic brains, which are common to comorbid epileptic disorders. Together, epilepsy and ASD are now estimated to affect more than 10% of the population worldwide and continue to be amongst the most costly to society. Although the prevalence rate of autism has dramatically increased during the past two decades, basic research has lagged behind due to a scarcity of human brain tissue for autism research. The information derived from these studies on mouse brain tissue will allow us to identify specific cellular and molecular targets for further targeted mechanistic studies on human autistic brains.