cmdtla.org - Saúde Tropical

Research Group Information (RG-LVT-Lisboa-750018-3141)

Designation:

Biotechnology

Principal Investigator:

Carlos Manuel Mendes Novo

Location of Group:

Instituto de Higiene e Medicina Tropical - Universidade Nova de Lisboa

Keywords:

Monoclonal antibody ,Biochemistry ,Protein engineering ,Applied Immunology

Funding, sources, dates

Funding of the research activity was obtained through the submission of projects to national and international funding agencies. At national level by submission of candidatures to FCT Agency, throughout the POCTI and PTDC programs, AGRO program from MADRP Ministry, IDEIA program from the Agency for the Development and Innovation (ADI) and at the international level to the INCO-DEV action of the 6º Framework Program.

The funding for human resources and training was obtained by submission to FCT of candidatures for PhD fellowship grants and by submission to PEPAP and IEFP programs of candidatures for professional training. At international level the funding was obtained from Leonardo Da Vinci (Lise-Meitner-School, Berlin, Germany), Marie Curie (Scottish Crop Research Institute, Invergowrie, Dundee Scotland), COST actions and Windsor Treaty fellowship grants.

During the period 2003-2007 the funding obtained by UTPAM, excluding staff salary, was: 407 992 Euros (61%) from Research projects, 204 390 Euros (31%) from PhD and other grants fellowships and 55 406 Euros (8%) from PIDDAC, in a total of 667 788 Euros.

[Information accessed: 01-11-2008 11:02:21 on www.fct.mctes.pt]
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Group Team

List of Researchers in the Group:

001. Ana Isabel Amaro Goncalves Domingos ( Cat.: Investigador Auxiliar Gr. Acad.: Doutoramento )

002. Carlos Manuel Mendes Novo ( Cat.: Investigador Auxiliar Gr. Acad.: Doutoramento )

List of Collaborators (w/o PhD):

001. ANA MARIA BUTTLE DE MENDONCA MOURAO POSSIDONIO DE ARMADA ( Cat.: Investigador Auxiliar Gr. Acad.: Mestrado )

002. Carla Correia Gonçalves da Costa ( Cat.: Não aplicável (bolseiro) Gr. Acad.: Licenciatura )

003. Cristina Isabel Correia de Almeida Costa ( Cat.: Não aplicável (bolseiro) Gr. Acad.: Mestrado )

004. Raquel de Sá da Silva Laires ( Cat.: Não aplicável (bolseiro) Gr. Acad.: Licenciatura )

005. Tiago Miguel Lopes Martins ( Cat.: Não aplicável (bolseiro) Gr. Acad.: Licenciatura )

Objectives & Achievements

Objectives:

Scientific Research on Biotechnology for Human and Veterinary health (Scientific Knowledge production)

Development of Human resources through Technical and University graduated and pos-graduated thesis

Technology transfer to companies through human resources skills development, analytical methods installation and optimization as well R&D activities through scientific projects in collaboration

Internationalization and networking activities. Participation on national and international networking, development of PhD University thesis and projects in collaboration with international research groups as well through acquisition and/or transfer of technical competences with different international groups

Main Achievements:

The main achievements under the CMDT activity were as follow:

Bovine Babesiosis: A new detection method based on PCR was developed for the molecular diagnosis of bovine babesiosis. Field samples from Mozambique were tested by a new method, and the results showed high prevalence of bovine babesiosis by Babesia bigemina and B. bovis. Babesial recombinant proteins were expressed in E. coli and the obtained proteins are being evaluated, for diagnosis purposes. as drug targets.

Malaria proteases: Cystein and aspartic proteases genes from Plasmodium chabaudi were sequenced (AC: AF427013, AY289110, AY289109) and recombinant protein produced in E. coli. Monoclonal antibodies were produced against recombinant proteases and used on western blotting analysis and immunofluorescence localization in different parasite life stages. One theoretical 3D model was also constructed by comparative modelling for the aspartic proteinase (PDB code: 1KBX)

Protein disulfide isomerase as therapeutic target: The genomic sequencing of DNA from P. chabaudi (AY769864) was carried out by our team as well its expression in E coli. Theoretical 3D models were also constructed by threading and comparative modelling (PDB codes: 1YK6, 1Y9N, 1Y9P)

Diagnosis of malaria in urine: Urine samples from Mozambique and Angola, were analysed by SDS/PAGE and immunoblot. A 37-40 kDa antigen was recognised by an anti-falciparum serum in just 50 % of the malaria patients urines collected in the presence of proteases inhibitors. This antigen wasn’t present in control urines. A parallel study has been carried out with a malaria mouse model. Mabs against P. berghei sporozoits were also produced.

Characterization of antigens in P. chabaudi: The results obtained using Monoclonal antibodies, phage display peptide library, IFA and computational approaches has identified an antigen present in all stages of the erythrocyte cycle of P. chabaudi parasite with a 235 kDa MW determined by SDS-PAGE

The results suggested that the recognized antigen in P. chabaudi by the Mab PcIIC6 cross react with P. falciparum. Combined results suggest that in P. falciparum the antigen would be Pf332. Preliminary "in vivo" studies in rodent model P. chabaudi, demonstrated that the Mab PcIIC6 reduce the progress of infection on a dose dependent manner at the initial stage of infection.

Trypanosome peptidase inhibitors: Monoclonal antibodies towards ISP2 and ICP were obtained and applied to immunolocalization on T. brucei. Mabs towards evansain, Oligo B and FL antigens were also obtained.

Group Productivity

Master and Ph.D. thesis completed

• Pesquisa de Hidratase de nitrilo em microrganismos. Caracterização genética do metabolismo de nitrilos em Agrobacterium tumefaciens. Pedro Lourenço, Biochemistry PhD, Biotechnology speciality, FCT_UNL, 2005
• Identificação e clonagem dos genes implicados na resistência ao tributiestanho em bactérias marinhas. Andreia Cruz. MsC in Molecular Microbiology. University of Aveiro, 2005.

Patents/prototypes (2000 ca.)

New recombinant gp36 protein comprises an ectopic polypeptide linked to a gp36 polypeptide or peptide fragment, useful as vaccines for detecting or diagnosing HIV-2 in a subject

Patent Number: WO2007141650-A2 Assignee: INST MEDICINA MOLECULAR

Inventor(s): TAVEIRA N; DE SOUSA BARROSO M H; MARCELINO J M

New HIV-2 peptide, e.g. gp36 glycoprotein or C2-C3 envelope protein, useful for diagnosing, detecting, treating or preventing an HIV-2 infection Patent Number: WO2007084021-A2; WO2007084021-A3 Assignee: INST MEDICINA MOLECULAR

Inventor(s): TAVEIRA N; DE SOUSA BARROSO M H; MARCELINO J M

Publications in peer review Journals

Martins, T.M., Domingos, A., Berry, C., Wyatt, D.M. (2006) The Activity and Inhibition of the Food Vacuole Plasmepsin from the Rodent Malaria Parasite Plasmodium chabaudi. Acta Tropica 97, 212–218. (IF 2.211; NC=3)

Martins, T.M., Novo, C., do Rosário, V.E., Domingos, A. (2003) Aspartic proteases from Plasmodium chabaudi: a model for human malaria. Acta Trópica 89, 1-12. (IF 1.336; NC=5)

Marcelino, J.M., Barroso, H., Gonçalves, F., Silva, S.M., Novo, C., Gomes, P., Camacho, R., Taveira, N. (2006) Use of a new Dual-Antigen Enzyme-Immunosorbent Assay to detect and characterize the Human Antibody Response to the Human Immunodeficiency virus type 2 envelope gp125 and gp36 glycoproteins. Journal of Clinical Microbiology, 44, 607-611. (IF 3.445; NC=)

Custódio, A.I., Cardoso, F.H., Félix, M.R.,. Clara, M.I., Novo, C. (2006) Monoclonal antibody to Olive Latent Vírus 1. Acta Virologica 50, 273-274. (IF 0.788; NC=1)

Salvador, S.M., Novo, C., Domingos, A. (2006) Evaluation of the presence of aspartic proteases from Centaurea calcitrapa during seed germination. Enzyme and Microbiol. Tech. 38, 893-898. (IF 1.897; NC=1)

Cardoso, F.H., Armada, A., Fonseca, A.M., Santos, M.T., Sequeira, J., Clemente, A., Sequeira, O., Novo, C. (2005) Sequences of the N-termini of coat proteins of Portuguese Zucchini yellow mosaic virus isolates and of an epitope recognized by a monoclonal antibody. Journal of Plant Pathology, 87, 229-232. (IF 0.647; NC=1)

Martins, S., Karmali, A., Andrade, J., Custodio, A., Serralheiro, M.L. (2005) Characterization of Monoclonal Antibodies Against Altered (T103I) Amidase From Pseudomonas aeruginosa. Mol Biotechnol. 30, 207-220. (IF 1.859; NC=4)

Lourenço, P.M.L., Almeida, T, Mendonça, D., Simões, F., Novo, C. (2004) Searching for nitrile hydratase using the Consensus-Degenerate Hybrid Oligonucleotide Primers strategy. Journal of Basic Microbiology 44, 203-214. (IF 0.651; NC=3)

Novo, C., Tata, R., Clemente, A., Brown, P.R. (2003) Burkholderia genome analysis reveals new enzymes belonging to the nitrilase superfamily. The amidase of Burkholderia cepacia (hospital isolate). Int. J. Biol. Macromol. 33, 175-182. (IF 1.427; NC=1)

Martins, T.M., Domingos, A., Novo, C., Lourenço, P.M.L. (2003) Effect of Agrobacterium rhizogenes infection on in vitro rooting of Vitis vinifera. Vitis 42, 159–161. (IF 1.012; NC=1)

Other publications National 

• Domingos, A., Gabriel, A., Silva Laires, R., do Rosário, V.E., Almeida, P.G., Novo, C., Silveira, H. (2004) Serine proteases involved in the mosquito immune response. 2nd Annual Meeting of the Portuguese Proteomic Network-Procura, Lisboa.
• Prata, S., Martins, T.M., Domingos, A., do Rosário, V.E., Novo, C. (2004) Protein disulfide isomerase as target for chemotherapy. Isolation and sequencing of the protein disulfide isomerase from Plasmodium chabaudi. PJ.46, XIV Congresso Nacional de Bioquímica, Vilamoura, Portugal.
• Nuno Taveira, José Marcelino, Helena Barroso, José Casanovas. Identificação de cinco casos de infecção por VIH-2 em Moçambique utilizando o novo teste ELISA-HIV2. Poster apresentado no Congresso Nacional dos Farmacêuticos 2007, Lisboa, 8 - 10 de Março de 2007.
• Rocha, C., Barroso, H., Bártolo, I., Marcelino., J, Rosado, L., Taveira, N. (2006) Evolução molecular do gene env do HIV-2 e colapso do sistema imunitário em doentes infectados por via vertical. Livro do 7 Congresso Virtual HIV/AIDS
• Gaspar, J., Custódio, A., Novo, C. (2006) Olive mild mosaic vírus antibodies from a phage display library, SI 3, XV Congresso Nacional de Bioquímica, Aveiro
• Morais, J.B., Martins, T.M., Marcelino, E., Cortes, H., Leitão, A., Novo, C. (2006) PDI is expressed in Besnoitia besnoiti. PI.15, XV Congresso Nacional de Bioquímica, Aveiro
• Marcelino, J., Doroana, M., Maltez, F., Rosado, L., Gomes, P., Nilsson, C., Taveira, N. (2006) Resposta humoral contra as glicoproteínas do invólucro gp125 e gp36 em doentes infectados por VIH-2: impacto da terapêutica antiretroviral. Poster P1.52, VIII Congresso Nacional de Doenças Infecciosas e 6º Congresso Nacional Sobre Sida, Porto.
• Rocha, C., Barroso, H., Bártolo, I., Marcelino, J., Rosado, L., Taveira, N. (2006) Evolução intra-hospedeiro do Env do VIH-2 na infecção vertical. Poster P1.19, VIII Congresso Nacional de Doenças Infecciosas e 6º Congresso Nacional Sobre Sida, Porto.
• Camacho, R., Oliveira, C., Martins, T, Reis, Y., Fazendeiro, I., Cortes, H., Leitão, A., Novo, C. (2005) Identificação de um gene putativo de isomerase dissulfureto (PDI) em Besnoitia besnoiti Congresso de Ciências Veterinárias, Poster 92, Lisboa
• Lopes, A., Teixeira e Costa, F., Carvalho, F., João Galvão, Mª, Novo, C. (2003) Detecção do depósito amilóide por cintigrafia com o componente P na polineuropatia amiloidótica familiar tipo português: Purificação do componente P. X Congresso Nacional de Biotecnologia-Biotec2003, Lisboa, Portugal.

Other publications International 

• Tiago M. Martins, Virgilio E. do Rosário, Luis Neves, Ana Domingos. Development of a new Hot-start PCR method for the detection of bovine Babesiosis in Mozambique. 3 rd general ICTTD Meeting, September 24-28, 2007, Zanzibar, Tanzânia
• Tiago M. Martins, Carlos Novo, Virgílio E. do Rosário, Ana Domingos. New cysteine proteases from the cattle parasite Babesia bigemina. Drug Development for Parasite Diseases - B22 Annual Congress, 2007, 10 – 13 June 2007, University of Dundee, Scotland, UK.
• Caldeira, R.L., Martins, T.M., Silveira, H., do Rosário, V., Novo, C., Domingos, A. (2006) Cystein Proteases from Plasmodium chabaudi an Important Target on Malaria Therapy, International Journal of Infectious Diseases , vol 10 - supl. 1: S298
• Caldeira, R., Martins, T., Silveira, H., do Rosário, V., Novo, C., Domingos, A. (2006) Chabaupain-1 a cystein protease can be detected in protein midgut extracts of Plasmodium infected anopheles mosquitoes. 3 rd Annual Joint Meeting Cost Action B22-Drug Discovery & Development for Parasitic Diseases, 1 a 4 Outubro, Atenas, Grécia
• Marcelino, J.M., Barroso, H., Gonçalves, F., Silva, S.M., Novo, C., Gomes, P., Camacho, R., Taveira, N. (2005) A sensitive and specific ELISA assay for the detection of the antibody response to the HIV-2 envelope glycoproteins in single and dual HIV infections. Poster (MoPe15.2C13), 3rd IAS Conference on HIV Pathogenesis and Treatment. Rio de Janeiro, Brasil.
• Pedro Borrego, José Marcelino, Cheila Rocha, Manuela Doroana, Fernando Maltez, Helena Barroso, Nuno Taveira.. Intra-patient molecular evolution of the env gene in HIV-2 infection. Poster P24 apresentado no XIII International Bioinformatics Workshop on Virus Evolution and Molecular Epidemiology, Lisboa, 2007.
• Nascimento, T, Cardoso, F, Rego, C., Oliveira, H. Presence of double-stranded RNA molecules in Cylindrocarpon liriodendri isolates infecting grapevine. Phytopathologia Mediterranea, 46,120. - COST Action 857, 4 st Annual Workshop Porticcio, Ajaccio, France, May 4-7 th, 2007.
• Custódio, A.I., Novo, C., Torrance, L, Ziegler, A. (2006) Single Chain Antibodies against Olive Trees Virus World Congress of International Association for Plant Tissue Culture and Biotechnology, Beijing, China
• Nascimento, T., Cardoso, F., Rego, C., Oliveira, H. (2006) Presence of double-stranded RNA molecules in Cylindrocarpon liriodendri isolates infecting grapevine. 5h International workshop on grapevine trunk disease, September, Califórnia, USA
• Rocha, C., Barroso, H., Bártolo, I., Marcelino, J., Rosado, L., Taveira, N. (2006) Genetic evolution of the HIV-2 env in a patient with fast disease progression. Poster X5-343, Keystone Symposia HIV Pathogenesis. Keystone Resort, Keystone, Colorado, EUA.

Organization of conferences

Proteases – PhD Program, Aveiro University, March 2007.

Humoral response as a marker of disease progression in HIV-2 infection. Conference at URIA/CPM/FFUL, June, Lisbon 2007.

Two Internal cycle conferences at Biotechnology Department of INETI in collaboration with the UBB Unity. 2005, 2006

Workshop about “Parasite Proteases” financed by the Windsor treaty- British Council with the participation of Colin Berry from the Cardiff University, UK.

Workshop about Monoclonal antibodies with the support of the Portuguese Society of Pharmaceutical Sciences with the participation of researchers from FFUL, FMV_UTL, DGV, INETI and Roche, 2006.

Conference about Crystalography. Margarida Archer from ITQB, INETI, 2004.

Industry contract research

Technology transfer is being done through PhD grant, with the company CERAMED on the field of the citotoxicity and immunologic response to medical devices composites; Through IDEIA project, on malaria diagnostic with ImunoStar company and through Lab facilities offer to DNAtech on the Veterinary pathologies diagnostic. There are ongoing contacts with other partners for submission of projects to the QREN program (Projects in co-promotion)

PhD fellowships grant

“Contribuição para o desenvolvimento de novos implantes biocompatíveis para regeneração óssea” Sofia Prata. (SFRH/BDE/15640/2006). Host institutions: UTPAM/INETI, Department of Materials Sciences, FCT/UNL and the CERAMED company. Supervisors: João Paulo Borges (FCT/UNL), Carlos Novo (INETI). Institution which confer the degree: FCT-UNL

Project

URMAL – Malaria diagnostic on urine samples (IDEIA program). (ImunoStar, INETI, CMDT_IHMT_UNL) 2006-2008.

Government/Organization contract research 

TRYPADVAC 2 - Development of an “anti-disease” vaccine and diagnostic tests for African trypanosomosis (6º PQ - INCO-DEV). (2005_2009) (http://trypadvac2.eventos.usb.ve/)

Cysteinic proteases from Plasmodium chabaudi, a animal modelfor human malaria: chemical and biochemical characterization (POCTI/SAU-ESP/57696/2004).

Malaria diagnostic in urine (IDEIA). (Agência de Inovação). (2006-2008).

Trypanosome brucei peptidase inhibitors. Imunolocalization, secretion and potential use as targets for therapy (PTDC/CVT/67086/2006)

The Proteases of Plasmodium chabaudi as targets for malária therapy, “design” of new inhibitors (POCTI/BME/43637/2002).

Large scale application of immunological methods to the detection and selection of Quercus suber producing high quality cork. Project nº 368 Agro program. (2004-2007) (INETI/EFN/FFUL/FloraSul)

Neutralization profiles of sera from HIV-2 infected individuals: relationship to viral load and to the genetic and phenotypic diversity of virus quasispecies (POCTI/ESP/48045/2002). (INETI/ADEIM)

Natural peptidase inhibitors of trypanosomatids “Collaboration on a grant form, Ref nº 1694” between the Wellcome Centre for Molecular Parasitology from Glasgow University (UK) and UTPAM/INETI (2007).

Protein disulfide isomerase as a target for besnoitiosis therapy. Molecular characterization and studies of its role in infection and host response (PTDC/CVT/65674/2006). (INETI/IICT/U. Évora)

Validação e aplicação em larga escala de um “kit” de diagnóstico multiviral (Agro Ação 8.1 proj 73). (2003-2005) (INETI/U. Évora/EAN)

Internationalization

Through participation on 6º FP project, COST actions, PhD mix fellowship grants, Leonardo da Vinci and Marie Curie fellowship grants and international networks. Preliminary contacts with other partners for candidature submission to the 7º FP are in progress

Projects

TRYPADVAC - (6º FP / INCO-DEV).(2005-2009), the FCT project PTDC/CVT/67086/2006 and the “Grant Ref nº 1694” from the WCMP Glasgow University, UK (2007)

Mix PhD fellowships grants

Raquel Laires (SFRH/BD/32110/2006) Supervisors: Jeremy C Mottram (Glasgow University), Carlos Novo (INETI), Luis Távora Tavira (CMDT-LA_IHMT_UNL). Institution witch confer the degree: IHMT_UNL

Cristina Costa (SFRH/BD/40223/2007) Supervisors: Tansy Hammarton (Glasgow University), Carlos Novo (INETI), Virgilio do Rosário (CMDT-LA_IHMT_UNL). Institution witch confer the degree: IHMT_UNL.

Other PhD

“Human neutralizing antibody (IgG and IgA) response against the human immunodeficiency virus type 2 (HIV-2): identification of neutralizing epitopes in primary virus isolates and production of human monoclonal antibodies against the envelope gp125 glycoprotein” José Marcelino. Supervisors: Rui Vitorino (FMUL), Nuno Taveira (ISCS do Sul), Charlotta Nilsson (SMI - Karolinska Institute, Suécia), Carlos Novo (INETI). Institution which confers the degree: FMUL._UL

“Produção e expressão de anticorpos recombinantes anti-Tobacco Necrosis Virus, para diagnóstico e indução de resistência em plantas de Nicotiana benthamiana e Olea europaea” Ana Isabel Custódio, (SFRH/BD/19040/2004). Supervisors: Ivone Clara (U. Évora), Carlos Novo (INETI). Institution which confer the degree: Évora. University. (Collaboration with the SCRI, Invergowrie, Dundee (UK), (5 months Marie Curie grant).

“Identificação de proteases como alvos de diagnóstico e terapia em babesiose bovina” Tiago Martins (SFRH/BD/19059/2004). Supervisors: Ana Domingos (INETI), Virgílio do Rosário (CMDT-IHMT), Luís Neves (Mondlane University, Maputo, Mozambique). Institution which confer the degree: IHMT_UNL.

Leonardo da Vinci fellowship grants

3 months stage of students from the Lise-Meitner-School, Berlin, Germany: Sabrina Lachman (2007), Marleen Herschel (2006), Markus Hensel (2005).

Other technical stages

Three stages on phage display library technology of Pongwit Bualombai from the Department of Diseases Control of the Public health Ministery of Thailand (2004 and 2005) and Pannada Dhepakson, from NIH, Thailand (2003)

Several stages of UTPAM members team at international Research institutions: Karolinska Institute, Sweden (2004, 2005, 2006); Scottish Crop Research Institute, Invergowrie, Dundee, UK (2005, 2006); University Eduardo Mondlane, Mozambique (2005); Cardiff University, UK (2003).

Future Research

Objectives:

To continue the actual research lines on Trypanosome peptidase inhibitors (6º FP TRYPADVAC and PTDC/CVT/67086/2006 projects and SFRH/BD/32110/2006); Babesiosis, by submission of a project candidature to FCT in collaboration with ITQB (Abel Oliva) as well through the submission of a mixed BD (SFRH/BD/48251/2008); Antigens from Plasmodium chabaudi through the submission of a project candidature to FCT and protein disulfide isomerise as target for therapy through the project PTDC/CVT/65674/2006 and the BD (SFRH/BD/31445/2006)

To develop the new following research lines:

“The role of humoral response in HIV-2 infection”

Abstract: Understanding how the IgG and IgA neutralizing and non-neutralizing antibodies evolves in HIV-2 infected individuals could provide new insights to explain the slow disease progression in HIV-2 positive patients and to help in development of an effective vaccine This research line has as main objectives: 1) to determine the role of autologous neutralizing antibody response in HIV-2 infected individuals; 2) to examine the epitope specificity of the serum neutralizing activity of IgG and IgA subtype in HIV-2 infected patients towards peptide epitopes in the C2V3 domains from the autologous primary isolate and 3) to develop new reagents that help in monitorization of HIV-2 infection.

Cell cycle and cytokinesis regulators in Trypanosoma brucei

Abstract: The cell biology of Trypanosoma. brucei is unusual and the mechanism of cytokinesis differs markedly from mammalian cells. It has previously been shown using RNAi that downregulation of PLK or MOB1 in bloodstream form T. brucei or TRACK in procyclic cells, inhibit cytokinesis at the level of furrow ingression. When RNAi of these proteins is induced, the population becomes enriched for post-mitotic cells, many of which contain furrows. This phenotype will be exploited in order to generate monoclonal antibodies against proteins involved in cytokinesis in T. brucei. Such monoclonal antibodies will not only be used as markers of trypanosome cytokinesis, but as tools to identify novel proteins involved in this process

Recombinant antibodies for therapy

Abstract: The recombinant antibody technology allowed to engineer the complex structure of an immunoglobulin in different formats, the most effective being the single-chain Fv (scFv). Also bispecific single-chain antibody fragments (biscFvs) by bridging target and effector cells results in target-cell destruction as reported in several models. Antibody expression in plants can be applied widely for research and diagnostic or therapy purposes

Parasite proteomic analysis for identification of new diagnostic/therapeutic molecules

Abstract: Proteomics to compare proteases profiles between infected and non-infected mosquitoes and identify key molecules/mechanisms that will contribute to a more efficient malaria control.

Proteomics of experimental animal model serum infected with P. chabaudi, Cryptosporidium parvum and Toxoplasma gondii in order to identify new target molecules for diagnostic.

Molecular and immunological approaches on the study of the prevalence of tick-transmitted diseases in Africa

Abstract: Ticks and tick–borne diseases (T&TBDs) are widespread in some African countries constituting a major obstacle to the development of a sound milk and meat industry. Epidemiological studies conducted so far highlighted the need for application of more specific and sensitive, reproducible and easy to perform techniques for diagnostic/prevalence studies.

Funding

The actual total funding for UTPAM (2008-2010) on the ongoing research line is circa 236 000 Euros. For new research lines (2009-2013) the funding and sources are as follows:

CELL CYCLE AND CYTOKINESIS REGULATORS IN TRYPANOSOMA BRUCEI

PhD fellowship Cristina Costa (SFRH/BD/40223/2007) in collaboration with the Wellcome Centre for Molecular Parasitology from Glasgow University (Tansy Hammarton) and the CMDT/IHMT. Actual funding: 29 570 Euros. In preparation one project candidature for submission to FCT.

RECOMBINANT ANTIBODIES (SCFV) FOR THERAPY

Submitted one PhD fellowship candidature (SFRH/BD/46558/2008). In preparation two project candidatures for submission to FCT. One on scFv towards Cryptosporidium parvum and the second on the use of a biscFv recombinant antibody for therapy, both in collaboration with the UEI de “Protozoários Oportunistas/VIH e Outras Protozooses”/UPMM/IHMT

THE ROLE OF HUMORAL RESPONSE IN HIV-2 INFECTION

This research line was supported by the project (POCTI/ESP/48045/2002) in collaboration with the ADEIM of FFUL. In preparation project candidatures for submission to FCT.

Parasite proteomic analysis for identification of new diagnostic/therapeutic molecules

In preparation project candidatures for submission to FCT:

On malaria proteases, in collaboration with the UEI Malaria (H.Silveira) and INSA; On serum analysis of P. chabaudi, Cryptosporidium parvum and Toxoplasma gondii infected animal models in collaboration between UTPAM/INETI, CMDT/IHMT, UEI “Protozoários Oportunistas/VIH e Outras Protozooses”/UPMM/IHMT and a international partner.

Molecular and immunological approaches on the study of the prevalence of tick-transmitted diseases in Africa

Expected to be supported by the Khartoum University (Sudan)

Previous publications in the area

Borrego P, Marcelino JM, Rocha C, Doroana M, Antunes F, Maltez F, Gomes P, Novo C, Barroso H, Taveira N. (2008) The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients . Retrovirology 5:78 (IF 4.04)

Marcelino JM, Barroso H, Gomes P, Maltez F, Rosado L, Doroana M, Nilsson C, Taveira N. (2008) Evolution of the envelope-specific antibody response in HIV-2 infection: C2V3C3-specific IgG response is a marker of disease progression. AIDS (accepted).

Martins TM, Pedro OC, Caldeira RA, do Rosário VE, Neves L., Domigos A. (2008) Detection of bovine babesiosis in Mozambique by a novel semi-nested hot-start PCR method. Veterinary Parasitology 153:225-239.

Marcelino JM, Barroso H, Gonçalves F, Silva SM, Novo C, Gomes P, Camacho R, Taveira N. (2006) Use of a new dual-antigen enzyme-linked immunosorbent assay to detect and characterize the human antibody response to the human immunodeficiency virus type 2 envelope gp125 and gp36 glycoproteins. J Clin Microbiol. 44: 607-11. (IF 3.445)

Custódio AI, Novo C, Torrance L, Ziegler A. (2006) Single Chain Antibodies against Olive Trees Virus World Congress of International Association for Plant Tissue Culture and Biotechnology, Beijing, China.

Custódio A, Cardoso F, Novo C, Felix MR, Clara I. (2003) Isolation of scFv from TOMLISON I+J antibody library against Olive Latent virus 1. X Congresso Nacional de Biotecnologia-Biotec2003, Lisboa, Portugal.

Marcelino JM, Novo C, Pereira JM, Picotez F, Clemente A, Taveira N. (2001) Production and Characterization of a Mouse Monoclonal Antibody against the Gag p26 Protein of Human Immunodeficiency Virus Type 2: Identification of a New Antigenic Epitope. AIDS Res and Hum Retroviruses 17:1279-1283. (IF 2.523)

Special Requirements

The main requirement is the establishment of full contracts with the actual PhD students after their final discussion in order that the knowledge and technical skills acquired do not be lost as well it could be applied to the development of research on these areas.

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