Sandra O'Neill, DCU

Dr. Sandra O'Neill, DCU

Dr. O'Neill

Dr Sandra O'Neill is a lecturer of Biosciences in the School of Nursing at Dublin City University. Having completed fours years nursing in England she pursued her interest in studying infectious diseases of humans, obtaining an Applied Biology degree at Brunel University, London, majoring in Parasite Immunology. This initiated an interest in understanding how parasitic worms (helminths) manipulate the host immune response to ensure its survival within its host. Continuing with this interest she returned to Ireland to complete a PhD in helminth immunology.

Currently she is managing a research team, which as part of the Molecular Parasitology Unit at DCU, is interested in identifying parasitic molecules that manipulate the protective immune response of the infected host.

Juvenile flukes migrating through liver tissue: Juvenile fluke gain entry into the host after the infectious metacercariae cysts are ingested on watercress or algae. The flukes can spend up to 8-12 weeks migrating through the liver tissue before it reaches the bile duct where it begins sexual reproduction. One of the objectives of our group is to understand why these parasites remain unharmed while migrating through the liver tissue despite the constant attack from the host immune effector cells.

Impact of parasites on world health

Infectious diseases caused by helminth parasites such as blood and liver flukes, gastrointestinal worms, cestodes and nematodes still remain one of the largest causes of death and morbidity in the developing world. Over 1.5 billion individuals are infected with helminth parasites and the majority of individuals harbour infections for life resulting in chronic disease. Furthermore recent evidence suggests that helminth infections make individuals more susceptible to pathogens such as HIV and tuberculosis. Helminth parasites are also the most prominent disease in animals and are associated with reduced weight loss, milk yields and wool production in livestock. Infection with helminth worms causes an estimated US$4 billions loss to the agriculture community annually. Despite the fact that over a quarter of the world's population are infected with these parasites there are no commercially produced vaccines to helminth infections in humans or animals. In addition there is an increased resistance by parasites to anti-helminth chemotherapies making the control of helminth parasitic infections increasingly difficult. Our research team is interested in understanding parasite-host relationships and are in the process of developing safe and effective vaccines and chemotherapies.

An individual in the chronic stages of Schistosomiasis: Over 200 million individuals are infected with the helminth parasite Schistosoma. Individuals become infected when they contact contaminated water sources. The parasite gains entry through the skin where it migrates to the liver tissue. In this parasitic disease liver failure occurs because the parasites releases million of eggs, which remain trapped in liver tissue causing extensive damage.

Immune responses to parasitic infections

Immune cells known as CD4+ T-helper (Th) cells play a critical role in regulating host immune response to invading pathogens. These cells are divided into two subsets based on the type of proteins they secrete. These proteins, known as cytokines, help recruit different cell types that attack invading pathogens. Viral and bacterial parasites induce the T-helper 1 subset that secretes IFN-g, IL-2 cytokines and recruit cells known as macrophages. In contrast helminth parasites induce the T-helper 2 subset that secrete cytokines IL-4, IL-5, IL-10, IL-13 and recruit cells known as eosinophils and mast cells. Over the course of evolution the T-helper 2 immune response specifically developed to attack invading helminth parasites. However parasites evolved to counteract this immune response by secreting molecules that disable it. To understand how the parasite evades the immune response we must identify these molecules and investigate their role in parasite biology and in immune evasion. Understanding these processes will allow us to develop appropriate therapies.

Schistosoma eggs trapped in the liver: Studies have shown that the liver pathology associated with Schistosoma infection is the result of eggs trapped in the liver tissue. Cells of the immune response were shown to contribute to this pathology. However not all individuals develop the fatal stages of the disease. Investigators are interested in learning why some individuals are more susceptible to chronic diseases than others and also identify which cells are important to the liver pathology.

Parasitic molecules - manipulators of host immunity

Our group has characterised a number of helminth molecules that are critical to its survival within the host. By exploiting recent developments in biotechnology my research group has produced these proteins in the laboratory. Using these recombinant molecules we intend to investigate mechanisms through which a parasite modulates the hosts immune response. Specifically one of these proteins called FheCL was shown to suppress the immune response to a T-helper 1 inducing bacteria and vaccine. Furthermore FheCL is involved in the acquisition of nutrients and aids the parasite's migration through liver tissue. By blocking the function of this molecule we can protect he host from the invading parasite and prevent the suppression of immune responses to bacterial and viral infections observed during helminth infections.

Living in a wormless world

Owing to adequate sanitation and public health services, helminth parasites have been largely eradicated as a biomedical problem in the developed world. In contrast the lack of these facilities in the developing world means that these infections remain highly endemic. Research by my group and others have advanced the understanding of parasite biology with a real potential for the first commercially available vaccine with the next ten years. However until the political and economic climate changes to support these scientific advances helminth worms will remain a public health problem in developing countries into the next millennium.

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