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LUNGMARK: Lung Cancer Biomarkers

We have discovered a group of 6 molecules, known as microRNA biomarkers, circulating in the bloodstream and associated with the presence of the deadliest form of lung cancer (adenocarcinoma; the single biggest cancer killer in the world). These can be tested for using simple PCR methods. LUNGMARK is available for licensing to a company who is keen to increase their exports with minimally-invasive cancer biomarkers. Non-Confidential Flyer


Beer Spoilage Prevention: Using natural antimicrobial peptides:

Beer spoilage is a major concern to every Master Brewer in the world. Contamination of brews with beer spoiling bacteria can lead to loss of entire batches of beer resulting in severe financial losses for the brewery. Industries sources indicate that “Product withdrawal of 3 weeks stock due to Lactobacillus contamination from a standard size brewery have resulted in losses of up to €3 million. Product withdrawal or recall can have major implications for Brand and business. Bacterial contamination is also a problem in all kinds of fermentations including bioethanol production. Non-Confidential Flyer


Mucosal Vaccines: Using a novel targeting molecule to create effective mucosal vaccines

Our novel mimetic of the lectin Ulex europaeus agglutinin-1 from the gorse bush, provides a means to develop effective mucosal vaccines.
Mucosal vaccination is an attractive option for controlling infectious disease since mucosal vaccines are cheaper to manufacture, easy to administer, and reduce the need for a ‘cold chain’ during transport. However, the development of mucosal vaccines is hampered by several factors including dilution of the vaccine in mucosal secretions, enzymatic degradation and inefficient uptake across epithelial barriers. Effectively targeting nanoparticulate vaccines to immune cells with the UEA-1 mimetic confers a number of advantages. Non-Confidential Flyer


Peptide Biomarkers: Fishing for novel proteins in breast cancer cells:

Cancer is the leading cause of death worldwide accounting for approximately 7 million deaths annually. Amongst women, breast cancer is the leading cause of cancer mortality. The holy grail of cancer research is to discover what makes cancer cells different from normal cells. One such difference lies in the proteins that are produced in cancer cell. We developed a method to identify a select pool of proteins from cancer cells and use this pool as 'bait' to fish for small molecules that recognise proteins unique to the cancer cell. The novel 'Recogniser' molecules identified by this approach represent a unique barcode of the cancer cell.Non-Confidential Flyer

 

Novel Combretastatin Pro-drugs

The modulation of microtubule function represents a significant target for the development of effective anti-tumor agents. The development of small molecule modulators of tubulin function in cancer cells is a highly important field of research. Researchers at Trinity College Dublin have synthesized novel Combretastatin (CA) analogue compounds and demonstrated tumor cell growth inhibition, and anti-tumor properties of the compounds which function as anti-mitotic, anti-proliferative agents over a comprehensive range of tumor cell lines at nanomolar concentrations.
At present, the leading combretastatin compound is combretastatin A4 disodium phosphate but` the clinical use of CA-4P may be hindered by instability, toxicity, drug resistance and limited bioavailability. CA-4 can isomerise to an inactive trans stilbene configuration hindering its use therapeutically. These novel CA compounds are effective in causing extensive and selective vascular damage and subsequent tumor growth delay and thus could be useful of the treatment of many cancers including breast cancer. Non-Confidential Flyer.

Dual Inhibitors of Tumor Angiogenesis & Vasculature

Tumor angiogenesis (blood vessel formation) and tumor vasculature have recently emerged as important targets in cancer treatment, applicable to multiple tumor types. Enzymes, specifically expressed in endothelial and sub-endothelial cells during tumor angiogenesis but not in normal vasculature represent an important target for inhibiting tumor growth and metastasis. The recent advance in identifying the role played by tubulin inhibitors in causing tumor vasculature shutdown also represents an attractive target for inhibiting tumor angiogenesis/vasculature. Researchers at Trinity College Dublin have developed novel hybrid inhibitors of tumor angiogenesis and vasculature with a dual mechanism of action, namely prevention of tubulin polymerization and enzyme inhibition. These novel compounds have the necessary built-in functionality to (i) inhibit endothelial cell proliferation and motility, (iii) prevent capillary tube formation, and (iv) cause tumour vasculature shutdown. Non-Confidential Flyer.

A Therapeutic For Inflammatory & Autoimmune Diseases

With nearly 20% of the developed world suffering or developing autoimmune and inflammatory related diseases and with no known cure, there is a growing and urgent need for more specific and effective therapeutics. Researchers from Trinity College Dublin have discovered a novel method of suppressing the induction of a specific subtype of T cell responses in vivo, which are fundamental players in autoimmune and inflammatory related diseases, such as multiple sclerosis (MS), rheumatoid arthritis (RA), ulcerative colitis and allergies. The technology is part of an earlier discovery which demonstrated that TCT, a virulence factor of Bordetella pertussis, can bind intracellular pathogen recognition receptors on innate immune cells. Parenteral administration of TCT suppressed the induction of T cells responses directed by dendritic cells in vitro and by direct administration with antigens in vivo. In animal models of human diseases, TCT attenuated acute graft-versus host disease and slowed the onset and clinical signs of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. More recently, the Researchers have demonstrated the immunosuppressive properties of another more potent TCT-like synthetic peptide molecule, which also has the ability to specifically significantly reduce the induction of a population of T cells in vitro and in vivo in the EAE model. Non-Confidential Flyer.

RNAi-mediated Blood Brain and Blood retina Barrier modulation

Many attempts have been made either to break the blood-brain barrier (BBB) or to design delivery systems that enable pharmacological agents to traverse the endothelial cells of brain capillaries. However, such attempts have been made without due consideration given to the structure of the tight junctions (TJs), which reduce the space between the plasma membranes of contacting endothelial cells to form a selective and highly regulatable barrier. Researchers at Trinity College Dublin have developed a novel platform technology that employs the use of interfering RNA (siRNA) to target tight junction proteins that are present at the BBB and BRB, such as claudins, occudins and zona occludens. Targeting TJ proteins induces both a transient and size-selective increase in permeability of the BBB and BRB, thus allowing for the delivery of small therapeutic molecules which would otherwise be excluded from the brain and retina if delivered systemically. Non-Confidential Flyer.

Novel Synthetic Route to Mecamylamine Analogues

Mecamylamine (Inversine ®) is a drug that was previously used to treat high blood pressure prior to the discovery and clinical use of beta-blockers. More recently mecamylamine (MA) has been reinvestigated as an anti-addiction agent and to treat conditions such as depression, ADHD, Tourette’s syndrome amongst others by action at nicotinic acetylcholine receptors. Despite such potential over numerous disease states only limited SAR information is available. Researchers at Trinity College Dublin have devised a novel synthetic route for the preparation of MA. The new synthetic route allows the preparation of numerous closely related analogues that were unavailable by previous methods. The analogues have been prepared with the aim of providing a more efficacious treatment with reduced side-effects. Preliminary electrophysiological testing of the initial compound library has shown that most compounds have similar or slightly improved activity with respect to MA itself but one compound in particular is a significantly more potent antagonist than MA. Non-Confidential Flyer.

Re-Engineered GFP

Green fluorescent Protein (GFP) is a fluorescent marker for gene expression commonly used in laboratories throughout industry and academia. Existing GFP has an inadvertent gene silencing property (see Corcoran et al. 2010) which is mitigated by this technology. Non-Confidential Flyer.

 

Smart Dental Splint; Managing Tooth-grinding Intelligently

Bruxism is a major dental problem, affecting at least 8-20% of the population.  If undiagnosed or improperly managed it can cause severe and costly damage to  teeth or expensive restorations (e.g. implants and crowns) and frequently causes facial pain. Presently there are no reliable, objective ways of confirming a diagnosis, assessing the severity of the condition or monitoring treatment effectiveness or compliance.  Bruxism patients are normally treated with a splint or nightguard, which protects the teeth.  2.5million splints are made annually in the USA alone, with a annual cost  of $1billion. The smart splint technology is a thin-film pressure sensor module that is integrated into the common dental splints in use today by dentists, to accurately monitor and diagnose bruxism. It replaces the current manual practice of imprecise assessment and associated repeat costs to the patient and insurer. Non-Confidential Flyer.

 

VIPER: a virally-derived peptide that blocks inflammation

Toll-like receptor 4 (TLR4) recognises pathogens leading to activation of the immune response, but also contributes to the development of a number of autoimmune and inflammatory diseases. As such, it has become a new target for drug development. Over millennia, viruses have optimised their ability to inhibit the immune response. Thus the Vaccinia virus protein A46 displays a remarkable ability to inhibit TLR4 function. We have exploited this viral know-how and developed an 11-amino acid peptide from A46, termed VIPER, which, when fused to a cell-penetrating delivery sequence, potently and specifically inhibits TLR4-mediated responses in vitro and in vivo. Non-Confidential Flyer.

 

Preterm Labour: A novel role for free fetal DNA in non-infectious preterm birth

Thirteen million preterm infants (before 37 weeks) are born annually.  In developed countries preterm labour resulting in delivery represents the vast majority of those infants that die within the 1st month of life.. No discovery made in the last 20 years, has resulted in a decrease in the premature birth rate. No treatment currently available has been shown to stop or reverse the process. Strikingly, in North America the preterm birth rate has increased from 7% in the 1980s to  an all time high of 12.9% in 2008.  All pregnant mothers have a certain amount of free fetal DNA that circulates in the maternal blood.  The amount increases as the mother approaches full term. In women delivering preterm, the amount of free fetal DNA is higher at an earlier stage of the pregnancy. We have made the novel discovery that this free fetal DNA sparks off an immune reaction in human cells through a receptor called Toll-like Receptor 9 (TLR-9). In our animal model there is a 69% still birth/inflammation from injection of fetal DNA.  This can be inhibited by the injection of specific TLR-9 inhibitors. Non-Confidential Flyer.

 

 

 


Last updated 21 February 2012 by innovation.centre@tcd.ie.