Molecular Parasitology

Parasitology

Globally, greater two billion people, one-quarter of the world’s population, suffer from parasitic diseases. These occur predominantly in low to middle income regions of the world, such as sub-Saharan Africa, Asia, and South America. Parasitic diseases cause high morbidity, particularly amongst children, reduce the economic potential of these regions, and compound the health and wellbeing issues related to poverty.
Within the agricultural community, parasitic infections are all too common - farmers spend over €2 billion per year on chemical treatments to protect their livestock. The emergence of drug-resistance parasites, as well as the impacts of climate change on parasite transmission, is causing major concern as we are now seeing an increase animal diseases. We use non-chemical treatments, such as vaccines, to protect our agricultural community, especially as the global population increases and the demand for food grows.
Our research team will develop novel diagnostic tests and vaccines for parasites to help farmers control and manage infection on the farm to reduce their reliance on chemical treatments. The ultimate aim is to benefit farmers - they need better means of detecting diseases on farms so that they can strategically, rather than randomly, treat their livestock. It saves money, effort and, in the long term, can help eradicate disease.
To develop new vaccines we need to understand the basic biology of the interaction between the parasite and its host – from this we can devise vaccines to break this relationship and protect the host, and we now have the molecular, bioinformatics and genetic tools to do this, as well as the technology to manufacture vaccines.

Liver Fluke Disease

Liver fluke disease is one of the most important worm parasites of livestock (about 85% of dairy cattle in Ireland are infected with the worm). The parasite is found on all continents of the world, and in many rural tropical regions (Egypt, Andean SA, Iran) it is also a major infection of humans. Drug resistant parasites have spread globally and species generally found in Europe (Fasciola hepatica) have hybridised with the tropical forms (Fasciola gigantica) to give rise to hybrids of unknown pathogenicity that have spread across Asia. Using many -omics technologies (genomics, transcriptomics, proteomics and glycomics) we are studying these parasites to understand their virulence mechanisms and modes of growth and development in the animal and human hosts. Funded by Science Foundation Ireland, we are currently developing diagnostic tests for disease detection and surveillance and vaccines for livestock with Teagasc, Athenry, Galway. We are also collaborating on animal and human liver fluke disease in Central Vietnam with Oxford University Clinical Research Unit, Ho Chi Ming, Vietnam.

Schistosomiasis and other tropical worms

Schistosome parasites (blood flukes) and several related liver flukes (Fasciola, Clonorchis, Opisthorchis, and Paragonimus species) are major public health problems that affect around 250 million people in over 70 tropical/sub-tropical countries (S. and C. America, Africa, Asia. These cause chronic diseases that impact heavily on morbidity and mortality as they can suppress the immune system, and impair fertility, growth, and cognitive development. A hallmark of these infections is their ability to avoid immune elimination and to live for decades with their host. They secure nutrients by secreting abundant amounts of proteases that digest host blood or tissues and protect themselves against immune attack by secreting anti-oxidants and immune modulatory molecules. Some of these immune modulators are small peptides that we call Helminth Defense Molecules (HDM). By understanding the various ways by which worms protect themselves from being eliminated by the host we should be able to devise strategies to counter these by vaccination.

Malaria

The single-celled parasite Plasmodium falciparum is the main cause of the most lethal form of malaria. In 2018, there was an estimated 228 million cases of malaria that resulted in ~405,000 deaths, predominantly in Sub-Saharan Africa and mainly in children and pregnant women. The global spread of drug-resistant parasites means that there is a constant battle to develop new treatments. Malaria parasites invade and grow inside red blood cells and degrade the internal protein haemoglobin into amino acids that they then use to build their own proteins. In our laboratory we study the enzymes (aminopeptidases) that play a role in the release of these amino acids. We are studying their structure, biochemistry and function with the view to developing new anti-malarial drugs that inhibit the enzymes and kill the malaria parasite.

COVID-19

COVID-19 is a major killer of humans and a threat to global stability. Our team are working on an SFI co-ordinated research and innovation project in rapid-response to the COVID-19 pandemic. In collaboration with our colleagues in NUI Maynooth, Prof Sean Doyle’s team, we are developing lab-based tests known as an ELISA and Immunoblots that can measure antibodies in blood and determine whether a person has been infected with SARS-CoV-2. Using molecular biology techniques, we have made several antigens, the features of the virus that prompt antibodies, and will use these as a basis for developing antibody tests that can be rolled out at scale to test large populations. The information gained is an essential element in the overall control measures employed to stop the spread of disease, as well as to understand its distribution, infectivity and epidemiology.

Sepsis and other inflammatory conditions

Parasites may be our foe, but they can also be our friends! The extraordinary high prevalence of worm infections in the world undoubtedly reflects their co-evolution with and adaptation to humans. One of the major factors related to their success is their ability to manipulate or suppress the host immune system to their advantage, preventing their elimination and accounting for their survival for up to 20 years in the host. On the other hand, the immune suppressive/regulatory mechanisms that worms use to protect themselves can also protect the host from over-reactivity of the immune system in the case of asthma, allergy and auto-immune disease. Therefore, maybe can we learn from worms and exploit their immunomodulatory tactics to our benefit and use the knowledge we gain from them in the treatment of dysregulated immune reactions, such as in multiple sclerosis (MS), Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA) or, indeed, in sepsis which affect over 17,000 people and kills 3,000 (one in five patients who develop sepsis) in Ireland each year? We are currently testing parasite molecules, such as the HDMs, in pre-clinical trials using model for different immune disorders.