Development of Novel Therapeutics

Dr Orla Howe, Dr A. Kellet and Dr Kevin Kavanagh. Biological mechanistic modes of action of novel copper (II) metallotherapeutic drugs.

Interdisciplinary collaboration between DIT, DCU and NUIM on novel metallotherapeutic drugs has led to the biological evaluation of a range of novel copper (II) metallotherapeutic drugs. In vitro cell and in vivo Galleria mellonella models have been instrumental in indicating the therapeutic potential of a range of copper (II) based metallodrugs. Tumour selective cytotoxicity, ROS induced apoptosis, avid DNA binding and nuclease cleaving properties to induce double strand DNA breaks have demonstrated their initial potential by in vitro analysis. More recently, the in vivo Galleria mellonella model has been used to identify the key genomic and proteomic cellular signalling cascades induced by selected metallotherapeutic drugs at very low active concentrations to elucidate their mechanistic mode of action and their potential as alternative chemotherapeutic drugs for future development.

 

Dr James Curtin, Dr Orla Howe and Dr Patrick Cullen. Non-thermal Plasma treatment of brain cancer.

Non-thermal atmospheric plasma (NTAP) generates reactive species such as superoxide and hydrogen peroxide that can induce targeted cytotoxicity. This is a very promising new technology for the treatment of a variety of cancers. We are using a range of carcinoma models to identify biomarkers for reactive species dependent and -independent cancer cell death induced by NTAP.

 

Dr Andrew Knox, Bioseutica BV. Establishing the Antimicrobial Activity of Ovotransferrin.

In 2006 the EU introduced bans on the use of antibiotic growth promoters (AGPs) in food animal production. However, due to lack of alternatives and non-existence of a centralised data repository of antibiotic use in every European country, this ban is still not implemented to the full extent. Banning nonessential antibiotic use in food animals is intended to reduce pools of resistance genes which may also become prevalent in humans as similar antibiotics are used in both cases. To date, high levels of cross-resistance in animals and humans have been observed with fluoroquinolone and cephalosporin families of antibiotics and several studies have shown the potential of resistant bacteria in moving from animal to animal and animal to human via direct contact or through consumption of contaminated food. Finding safe and effective alternatives to traditional antibiotics will allow animal food producers to retain animal health and growth aspects of antibiotics without the danger associated with their use. Bioseutica BV with collaborators have established the efficacy of use of ovotransferrin, an egg white major protein, as a natural alternative to antibiotics normally used during fattening cycles of chicken broiler, turkeys and potentially other birds. The specific antimicrobial mechanism of ovotransferrin from initial investigation appears to act through the bacterial type III secretion system, however work is needed to further elucidate the mechanism of action. At the core of this IRC funded research (PhD candidate - Thomas Butler) is firstly the application of bioinformatic, cheminformatic and biochemical methods to establish the true mechanism of antimicrobial action of ovotransferrin, and secondly, to identify previously unknown related proteins which may have novel pathogenic action. 

 

Professor Gary Henehan and Dr Barry Ryan. Applied Bioconversion and Enzymology.

Dr Ryan and Prof. Henehan are engaged in the application of protein chemistry, enzymology and molecular biology in a variety of biomedical and biotechnological applications. Currently, one major research strand is focussed on understanding the regulation of the voltage gated shaker potassium channel. The beta subunit of this channel  is involved in moderating potassium ion flux. This channel has been shown to be important in a number of convulsive disorders.  In addition, group members are examining the use of novel lipase and glucosidase enzymes for carrying out specific biotransformations. Recently researchers within the group have shown that a nanoparticle immobilised beta glucosidase from Streptomyces griseus  is an efficient catalyst for the synthesis of a family of alkyl- and aryl-β-D-glucosides. Reasearch in ongoing within the group into the application of novel lipases from Amycolatopsis mediterranei for commercial purposes. 

 

Dr Greg Byrne. Obesity and the immune system.

Dr. Byrne has a long-standing collaboration with the Obesity Research Group in St. Vincent’s Hospital and is involved in projects investigating immune dysregulation in obesity. Current goals include the establishment of obesity research in ESHI with a view to further examine how obesity affects the immune system and how therapies may ameliorate obesity-related comorbidities.

 

Dr Oscar MacAnaney. Cardiovascular physiology and exercise physiology.

Arterial stiffness is a key determinant of systolic blood pressure and pulse pressure. It therefore has a key influence on cardiovascular disease. A greater understanding of the factors that may accelerate or attenuate premature vascular stiffening would be of great benefit for the treatment and prevention of cardiovascular disease and may open up new therapeutic approaches.

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