MOLECULAR IMMUNOLOGY RESEARCH GROUP

COMPARATIVE GENOMICS CENTRE

Comparative Genomics Centre,
Molecular Sciences Bldg 21, James Cook University,
Townsville, 4811, Queensland, Australia
Telephone: 61-7-4781 5463 Fax:  61-7-4781 6078
Email: Andreas.Lopata@jcu.edu.au

CONTENTS:



RESEARCH OVERVIEW:

    The Molecular Immunology Research group at the Comparative Genomics Centre encompasses various research areas in the field of human health, allergy and application in marine biotechnology.

Our research focuses on the health effects of natural and recombinant seafood proteins and understanding the underlying immunological reactions on molecular and cellular level; the molecular modification of allergenic proteins and the development of improved and novel diagnostic approaches towards save immunotherapy.


Main Research Areas:


Shellfish allergy – Towards better diagnostics and future therapeutics
Background
    There is currently a worldwide epidemic of allergy with, in particular, a rapid increase in food allergies and anaphylaxis in Australia. Although less prevalent than respiratory allergy, food allergy poses a grater threat to human health since trace amounts of food can provoke life-threatening anaphylaxis. Allergies to food affect up to 4 percent of adults and 8 percent of children and currently no curative or prophylactic treatment is available for food allergy. The only available treatment is avoidance, in conjunction with rescue medication in case of accidental exposure. Most food allergies are chronic life-long diseases that are always potentially life-threatening.
    Most allergic reactions to foods can be attributed to relatively few food groups that include shellfish. Seafood forms an important protein source in Australia as well as being important to our national psyche. The strong move to healthier eating habits and increased levels of consumption of seafood has resulted in more frequent reports of allergy-associated health problems. Very few of the proteins that trigger these reactions (called allergens) have been characterised in seafood, including shellfish, at molecular level. The increase in prevalence of food allergy in Australia and its potential fatality requires increased efforts to develop more specific diagnostic assays as well as effective therapies and prophylactic measures.
The current study is the first in Australia to investigate anaphylaxis to crustacean food allergens, produce specific diagnostic tools and analyse the allergenicity of modified natural and recombinant allergens using cutting edge molecular and cellular approaches.

Research aim
•    To identify and characterise novel and clinical important allergenic proteins
•    To produce recombinant allergens for improved diagnosis and immunotherapy using molecular biological techniques.
•    To evaluate the allergenicity of natural and recombinant allergens
•    To evaluate the distribution of these new proteins among crustaceans species in Oceania

Applications
•    Evaluation of the species-specific allergenicity of crustacean
•    Identification of crustacean allergens for labelling of food products
•    Improved diagnosis of sensitised and allergic patients
•    Immunotherapeutics for shellfish allergy

Detection and identification of novel allergens in Australian Fish
Background
    Few fish allergens have been characterised on molecular level and only parvalbumin, a small calcium binding protein has been recognized as the major allergen in most investigated fish species. The goal of this research effort is to increase biochemical and immunological knowledge of fish allergens and to identify, purify and characterize parvalbumin isoforms from important fish species produced and consumed in Australia. These studies will subsequently foster development of advanced diagnostic applications and ultimately, modification of these proteins to produce safe and specific immunotherapies for allergic individuals.

Research aim
•    To identify and characterise novel and clinical important allergenic proteins such as parvalbumin and collagen
•    To produce recombinant allergens for improved diagnosis and immunotherapy using molecular biological techniques.
•    To evaluate the allergenicity of natural and recombinant allergens
•    To evaluate the distribution of these allergenic proteins among fish species in Oceania

Applications
•    Evaluation of the species specific allergenicity of fish
•    Identification of fish allergens for labelling of food products
•    Improved diagnostics of allergenic patients

Nanoparticles, Chitosan and the immune system

    Nanoparticles (NPs) are a subset of nano-materials that defined as a single particle with a diameter below 100. Nanoparticles represent one of the most promising technologies of the 21 st century, and have been considered to be a new industrial revolution. The application of nano-materials ranges from vaccine delivery, to sunscreens, foods and antimicrobial agents. Australia has the highest rate of skin cancer in the world, and applications of sunscreens are very important to protect the skin from ultraviolet light damage. About 1,200 sunscreens are authorised in Australia by the Australian Therapeutic Goods Administration (TGA). Approximately half of these sunscreens contain Zinc oxide NPs or Titania NPs because of their ability to filter all UV light from sun, giving higher protection than other materials. While their is an ever increasing application of NP, their is little information on their immunogenic and toxic effects.To address the risks from application of nanomaterials, the toxicity and inflammation responses to nanomaterials are assessed in vitro and in vivo studies.

Organic chitosan nanoparticles for improved vaccination therapy
Chitin and chitosan are among the emerging materials which are being developed and applied widely in many industrial fields due to their biocompatibility, biodegradability, non-toxicity and adsorption properties. Chitin is a linear polysaccharide consisting of (1-4)-linked 2-acetamido-2-deoxy-β-D-glucopyranose while chitosan is a deacetylated derivative of chitin. Existing in various and abundant biological sources such as crustaceans and insects, chitin is produced in nature in high quantity, making it the second most abundant polysaccharide on earth. Crustacean shell waste contains 20 - 30% of chitin which can be extracted to be a more valuable product. Chitin and chitosan have been applied in biotechnology, food, medical field, cosmetics, environment and agriculture. In the food industry, they have been used as antimicrobial agents (bactericide and fungicide), edible films (active packaging, reverse osmosis membranes) and for nutritional quality (dietary fiber). The main obstacle to apply shellfish chitin and chitosan is the presence of residual shell fish proteins which can cause allergic reactions in people sensitive to seafood.
Furthermore, Chitin derivates have been shown to be potent stimulators for non-specific host responses to bacterial and viral infections. However, recent studies documented also pro-inflammatory affect by eliciting an allergy like response to foreign proteins. Accountable for these reactions are probably size-dependent pathogen-associated molecular patterns that stimulate receptors of the innate immune system, thereby stimulating the production of pro- and anti-inflammatory cytokines. Chitin and Chitosan have therefore received recent attention in vaccine research for their ability to stimulate a range of immune responses, depending on the size of this polysaccharide molecule. Our approach provides strict size control of both the chitosan molecules and their nanoparticle (NP) preparations, needed for developing its utilisation for vaccines and immunotherapy through stimulation of a favourable viral like response (Th1), rather than allergic response (Th2).

    These studies will contribute to the development of new nanomaterials with lower toxicity and greater therapeutic potential, and help identify potential biomarkers to assess the health hazard to nanomaterials.

Characterization of immune modulating proteins in the neglected tropical food-borne parasite Anisakis, a common nematode in Australian fish

Background
    Parasites, such as roundworms (nematodes) and flatworms have serious effects on fish health and can cause major economic losses due to deaths and the condemnation of infected fish. Some parasites such as Anisakis can also be transmitted to humans during ingestion of undercooked fish, causing major clinical disease. Anisakid nematodes are highly significant pathogens of fish and are very difficult to control because of the nature of their life cycles. In spite of their substantial negative impact on fish health and fish production in a range of countries around the world, virtually nothing is known about them or their impact on the fish industry in Australia. To provide a foundation for the present project, a recent preliminary study (using classical and molecular methods) was undertaken on a range of fishes from the Australian waters. The study revealed that numerous species of anisakid nematodes were prevalent in fish of commercial importance. Furthermore, environmental changes have direct affects on the population of marine life, i.e., the population of definitive and intermediate hosts of anisakid nematodes, which in turn has impact on the occurrence and prevalence of these nematodes.

    In recent decades, anisakid nematodes have attracted increasing attentions as a result of sharp increases in human infections world wide called Anisakiasis. In addition allergic sensitisation to allergenic proteins from Anisakis are frequently reported due to ingestion of contaminated seafood. Our group revealed an unexpectedly high risk of hypersensitivity to the parasite Anisakis pegreffii among fish processing workers. Subsequently we have developed a murine model investigating possible exposure routes as well as the key immunological mechanisms involved in the allergic reaction. Research into the allergenic proteins of Anisakis and the subsequent immunological reactions of this Neglected Tropical Parasite will provide the knowledge for improved diagnostics and treatment of this unusual allergic reaction to a food borne parasite.

Research aim



STAFF:

Group Head:

Research Staff
Graduate Students


POSITIONS IN THE MOLECULAR IMMUNOLOGY RESEARCH GROUP:

Postgraduate
Students interested in undertaking a PhD or Masters project in the Molecular Immunology Research Group should contact Anderas Lopata to discuss projects of mutual interest. Most higher degrees students would be expected to eligible for a scholarship through the Australian Postgraduate Award (APA) scheme, the James Cook University Postgraduate Research Scholarship or an equivalent national or international scholarship.

The Australian Postgraduate Award (APA) and James Cook University Postgraduate Research Scholarship (JCUPRS) are open to applicants with, or who expect to hold, a first class honours degree or equivalent by the end of the year and who wish to undertake full-time research Masters or PhD program. In 2010 the stipends for an APA were $22,500 pa (full time) or $12,176 (part-time). APA applicants must be Australian citizens or have been granted permanent resident status and lived in Australia continuously for 12 months prior to receiving the award; Information and application forms can be obtained from the Graduate Research School.  Closing Date: 31 October of each year.

Honours

Students who have completed their undergraduate training in a BSc, BBiomedSc, BMedlabSc or equivalent program and are interested in participating in the Biochemistry and Molecular Biology Honours Program are encouraged to contact Anderas Lopata for a description of currently available projects. Honours studies require a full-time commitment for one year (two semesters) and can start in either February or August.Follow this link for details.


Undergraduate

There are two main opportunities for undergraduates to participate in the ongoing research of the Molecular Immunology Research Group

Students enrolled in BC3203 (Special Topics in Biochemistry and Molecular Biology - second semester) could ask that they undertake their research project in the Molecular Immunology Laboratory.

Students can apply for a Comparative Genomics Centre Vacation Scholar Award. The successful applicants receive instruction in the latest recombinant DNA and genetics techniques, receiving a stipend of $200 per week for a full-time commitment of between 6 and 10 weeks over the summer break. Applications for the CGC Vacation Studentships are announced in September each year and close in late October. Contact Anderas Lopata for further details
 


RECENT PUBLICATIONS:

1.    van der Ventel, Michelle L., Nieuwenhuizen, Natalie E., Kirstein, Frank, Hikuam, Christoph, Jeebhay, Mohamed F., Swoboda, Ines, Brombacher, Frank, and Lopata, Andreas L. (2011) Differential responses to natural and recombinant allergens in a murine model of fish allergy. Molecular Immunology, 48 (4). pp. 637-646.

2.   Shamsi, Shokoofeh, Eisenbarth, Albert, Saptarshi, Shruti, Beveridge, Ian, Gasser, Robin B., and Lopata, Andreas L. (2010) Occurrence and abundance of anisakid nematode larvae in five species of fish from southern Australian waters. Parasitology Research, Epub ahead of print . pp. 1-8.

3.   Horsnell, W.G.C., Vira, A., Kirstein, F., Mearns, H., Hoving, J.C., Cutler, A.J., Dewals, B., Myburgh, E., Kimberg, M., Arendse, B., White, N,, Lopata, A., Burger, P.E., and Brombacher, F. (2011) IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunology, 4 . pp. 83-92.

4.   Lopata, A.L., O'Hehir, R.E., and Lehrer, S.B. (2010) Shellfish allergy. Clinical & Experimental Allergy, 40 (6). pp. 850-858. (Invited Review)

5.   Kirstein, Frank, Horsnell, William G.C., Kuperman, Douglas A., Huang, Xiaozhu, Erle, David J., Lopata, Andreas L., and Brombacher, Frank (2010) Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma. Journal of Allergy and Clinical Immunology, 126 (2). pp. 347-354.

6.    Kirstein, Frank, Horsnell, William G. C., Nieuwenhuizen, Natalie, Ryffel, Bernhard, Lopata, Andreas L., and Brombacher, Frank (2010) Anisakis pegreffii-induced airway hyperresponsiveness is mediated by gamma interferon in the absence of interleukin-4 receptor alpha responsiveness. Infection and Immunity, 78 (9). pp. 4077-4086

7.   Rahman, Anas M. Abdel, Kamath, Sandip D., Lopata, Andreas, Robinson, John J., and Helleur, Robert J. (2010) Biomolecular characterization of allergenic proteins in snow crab (Chionoecetes opilio) and de novo sequencing of the second allergen arginine kinase using tandem mass spectrometry. Journal of Proteomics, 74 (2). pp. 231-241.

8.   Rahman, Anas M. Abdel, Kamath, Sandip, Lopata, Andreas L., and Helleur, Robert J. (2010) Analysis of the allergenic proteins in black tiger prawn (Penaeus monodon) and characterization of the major allergen tropomyosin using mass spectrometry. Rapid Communications in Mass Spectrometry, 24 (16). pp. 2462-2470.

9.   Rahman, Anas M.Abdel, Lopata, Andreas L., O'Hehir, Robyn E., John J. Robinson, John J., Banoub, Joseph H., and Helleur, Robert J. (2010) Characterization and de novo sequencing of snow crab tropomyosin enzymatic peptides by both electrospary ionization and matrix-assisted laser desorption ionization QqToF tandem mass spectrometry. Journal of Mass Spectrometry, 45 (4). pp. 372-381.

10.   Rahman, Anas M.Abdel, Lopata, Andreas L., O'Hehir, Robyn E., John J. Robinson, John J., Banoub, Joseph H., and Helleur, Robert J. (2010) Characterization and de novo sequencing of snow crab tropomyosin enzymatic peptides by both electrospary ionization and matrix-assisted laser desorption ionization QqToF tandem mass spectrometry. Journal of Mass Spectrometry, 45 (4). pp. 372-381.

11.   Lopata, Andreas L., and Lehrer, Samuel B (2009) New insights into seafood allergy. Current Opinion in Allergy & Clinical Immunology, 9 (3). pp. 270-277. (Invited Review)

12.    Nieuwenhuizen, N., Herbert, D.R., Brombacher, F., and Lopata, A.L. (2009) Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by Anisakis. Allergy, 64 (9). pp. 1309-1318.


LINKS:


Autoimmunity Research Group, Medical Genomics Rseearch Group, James Cook University, Key words: Immunology, immune, immunogenetics, disease, risk, vaccine, Genetics, Genomics, Phenomics, Proteinomics, Gene, Autoimmune diabetes, Type 1 diabetes mellitus, childhood diabetes, lupus, systemic lupus erythematosus, haemolytic anaemia, hemolytic anemia, Coombs' test, antinuclear antibodies, renal failure, glomerulonephritis, gastritis, type A gastritis, pernicious anemia, immunology, popular science, biology.