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| Sept 2003 | Gregory Noland
Host Response to Malaria and Helminth Co-Infection: Implications for Natural and Vaccine-Induced Immunity Aims
1. Evaluate host response to malaria during intestinal helminth co-infection 2. Compare relative malaria transmission potential between trematode-co-infected and malaria-only-infected mice 3. Characterize immunologic basis of interactions between intestinal trematodes and malaria parasites 4. Evaluate protection conferred by two candidate malaria vaccines in helminth-infected mice
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| Sept 2004 | Bamini Jayabalasingham
Elucidating the Molecular Function of Plasmodium falciparum Sexual Stage-Specific Protein Pfg27 Aims
1. Identify proteins with which Pfg27 interacts during the process of gametocytogenesis 2. Characterize the nature of the interaction between Pfg27 and interacting protein(s) 3. Investigate the possible role of Pfg27 in translational regulation in P. falciparum
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| Rebekah J. Kent
Malaria Transmission in Macha, Zambia: Entomological Inoculation Rates of Anopheles arabiensis and Anopheles funestus S.S and Vectorial Capacity of An. arabiensis Aims
1. Determine the relative importance of An. arabiensis and An. funestus to P. falciparum transmission in Macha by comparison of their entomological inoculation rates 2. Describe the blood feeding behavior of An. arabiensis in Macha 3. Estimate the efficiency of P. falciparum transmission by An. arabiensis
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| Sept 2005 | Ralph LeBlanc, MD, MPH
Development of a Malaria Transmission-Blocking Mono-and Multivalent Vaccine (TBV) Based on Pfs230, Pfs48/45 and Pfs25 Aims
1. To determine the immunogenicity of selected antigens by ELISA, IFA and immunoprecipitation (I.P.) 2. To assess functional transmission-blocking activity (TBA) by gamete lysis and membrane feeding assay (MFA) 3. To evaluate combinations of pre- and post-fertilization antigens in a multiple-antigen vaccine 4. To evaluate natural boosting potential of immune responses primed by DNA plasmid vaccine |
| Adam Ruben
Thermodynamic Characterization of Plasmepsin Family Inhibitors Adaptable against Multiple Targets Aims
1. Continue designing and screening potential inhibitors of Plm II 2. Continue to determine the Ki of selected inhibitors against secondary targets Plm I and Plm IV 3. Crystallize Plms in complex with selected inhibitors 4. Based on the results of Specific Aims 1-3, identify candidates for erythrocyte assays. Use the results of those assays to relate structural and thermodynamic properties with in vitro function 5. Identify inhibitors to test in mouse and monkey models
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March 2006 | Michael Overstreet
Crosstalk between CD4+ T cells and CD8+ T cells in Immunity to Malaria Aims
1. Examine crosstalk between transgenic CD4+ T cells and CD8+ T cells in response to irradiated sporozoites using an adoptive transfer model 2. Examine CD8+ T cells behavior in response to peptide immunization in presence or absence of CD4+ T cell activation
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| Sept 2007 | Maroya Spalding
The Role of Lipoate Metabolism in P. falciparum Survival Aims
1. Investigate whether lipoate synthesis is essential in the apicoplast through conditional disruption of lipoylation in this organelle and to use lipoate-disrupted parasites to determine the relationship between lipoate synthesis and fatty acid synthesis 2. To investigate whether lipoate scavenging is essential in the mitochondrion and the cytosol through conditional disruption of lipoylation, and if lipoate scavenging is essential in the cytosol, to identify the lipoylated protein(s) in this subcellular compartment
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| July 2009 | Ifeanyi Anidi
Malaria and Lung Macrophages Aims
1. To definite the phenotypic and functional consequences that malaria infection has on the lung-derived macrophages 2. To determine the role that lung macrophages play in the pathogenesis of pulmonary malaria
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January 2010 | Daniel Lagasse
The role of lung macrophages in the control of malaria-induced pulmonary inflammation Aims
1. Dynamics of immune cell influx into the lungs upon malaria infection 2. Selective depletion of lung macrophages 3. Selective depletion of lung macrophages during P. berghei infection 4. Adoptive transfer of macrophages into the lungs |
| Katy Shaw
Genetic Analysis of Plasmodium falciparum Gametocytogenesis Aims
1. Transposon-mediated mutagenesis and screening for genes involved in gametocytogenesis 2. Interesting genes identified by the mutagenesis screen 3. Hypothesis about the function of Class I genes |
| Eva Tse
Migration and Residency of Antigen Specific Memory CD8+ T cells in the Liver Aims
1. To characterize the expression pattern of homing and adhesion molecules on antigen specific CD8+ T cells in the liver 2. To investigate the functional role of selected homing and adhesion molecules of antigen specific CD8+ T cells in the liver 3. To investigate the proliferation, circulation and renewal properties of memory CD8+ T cells establishing residence in the liver Background and Significance: Our laboratory has demonstrated that the priming of antigen specific CD8+ T cells first occurs at skin
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| January 2011 | Jinxia Ma
Development of efficient anti-malaria vaccines
Aims
1. Analysis of susceptibility of parasite-infected hepatocytes to granzyme B
2. Identification of mechanisms of resistance to perforin |
| Slavica Pavlovic-Djuranovic
Biological comparison between chimpanzee Plasmodium reichenowi and human Plasmodium falciparum
Aims
1. Developing in vitro culturing conditions for P. reichenowi in chimpanzee and human erythrocytes
2. Cultivation of P. reichenowi gametocytes for mosquito infectivity studies
3. Identify differences between P. falciparum and P. reichenowi using comparative transcriptional analysis
4. Develop in vitro culturing conditions for P. falciparum isolated from bonobo chimpanzees |
| Sibao Wang
Engineering symbiotic bacteria as a delivery system to block Plasmodium transmission by the mosquito
Aims
1. Select for bacteria that are well adapted to the mosquito midgut and are vertically transmitted
2. Engineer symbiotic bacteria to secret anti-malarial effector molecules
3. Test blocking efficiency of effector molecules produced by the engineered bacteria
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| January 2012 | Krista Matthews
Characterization of Plasmodium falciparum ELO3 in fatty acid elongation and its role in gametocytogenesis
Aims
1. Determine the role of ELO3 and its protein domains in gametocytogenesis using reverse genetics
2. Characterize the localization, elongase activity and substrate specificity of ELO3 |
| Andrea Radtke
The induction of protective CD8+ T cells against Plasmodium liver stages
Aims
1. To determine the role of skin and lymph node resident DCs in the induction of protective CD8+ T cell responses
2. To characterize the location and kinetics of CD8+ T cell priming in skin-draining lymph nodes
3. To investigate the innate immune signaling pathways required for inducing protective CD8+ T cell responses
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| Sept 2004 | Jeff Zhiqiang Lu, PhD
Structure and Inhibition Studies of Plasmodium falciparum KAS Enzymes Aims
1. To investigate the mode of action of PfKASIII inhibitors using biochemical techniques 2. To study the activity of PkFASI/II and test thiolactomycin and the PfKASIII inhibitors for activity against this enzyme 3. To structurally characterize the atomic level interactions of novel KAS inhibitors with PfKASIII enzyme
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| Sept 2005 | Nazneen Bano
Identification of the Host Cellular Pathway/s and Parasite Transporter/s Involved in Host Cholesterol Trafficking to Intrahepatic Plasmodium Aims
1. Identification of the host cellular pathways mediating cholesterol delivery from host cell to intrahepatic parasites 2. Functional analysis of the role Plasmodium ABCG1 transporter homologues in parasite cholesterol homeostasis
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| March 2006 | Debabani Chowdhury
Evaluation of B cell Responses against Plasmodium falciparum Transmission-blocking Vaccine Antigen (Pfs25) in Naive and Helminth-infected Mice Aims
1. To evaluate the efficacy of Pfs25 DNA vaccine in production of memory B cells and long-lasting plasma cell (LLPC) responses 2. To characterize the effectiveness of Pfs25 DNA vaccine in generation of memory B cells and LLPC responses, when the host (mice) is pre-infected with the helminth Heligmosomoides polygyrus (Hp) 3. To determine the formatin of germinal center (GC) in response to Pfs25 DNA vaccine in mice, which are uninfected or pre-infected with Hp
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| January 2006 | Stefan Kanzok
Genetic Analysis of Plasmodium falciparum Gametocyte Formation Aims
1. Gametocyte reporter strain 2. Transposon-mediated mutagenesis
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| March 2006 | Zhiyong Xi
The role of Anopheles gambiae MD2-like Genes in Innate Immune Defense Against the Human Malaria Parasite Aims
1. Determination of expression patterns upon infection 2. Determination of defense specificity 3. Assessing immune pathway regulatory functions of AGMLs 4. Assessing the interaction of AGMLs with plasmodium
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| January 2007 | Abhai Tripathi
Antigen Presentation Following Infection with Malaria Sporozoites Aims
1. Identification of dendritic cell subsets involved in presentation of sporozoite antigens to CD8+ T cells 2. Examine the role of innate immune system components in the development of CD8+ T cell responses
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| January 2008 | Sung-Jae Cha Aims
1. Identification and characterization of sporozoite ligands for Kupffer cell invasion 2. Identification and characterization of putative Kupffer cell receptors 3. Identification and characterization of human orthologs of Kupffer cell invasion |
| Ian Cockburn Aim
To identify the DCs that present sporozoite antigens to CD8 T cells and how the DC-T cell interactions are influenced by innate responses
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| October 2008 | Gabriel Brandt
Plastid DNA Replication in P. falciparum Aims
1. Production of apicoplast replication proteins: Express and purify the apicoplast-targeted polyprotein Prex in its full-length form, along with its helicase, primase, helicase-primase and polymerase domains. Express and purify the putative apicoplast single-stranded DNA binding protein 2. Begin reconstitution of plastid genomic replication in vitro: Examine, using mini-circle models of the replication fork, the ability of the helicase-primase and polymerase domains to replicate DNA. Determine the effect of helicase activity and single-stranded DNA binding proteins on polymerase activity 3. Undertake structural studies of the apicoplast replication proteins: Purify and concentrate Prex helicase, primase, helicase/primase and polymerase domains. Screen for crystallization conditions using sparse matrix methods and liquid-handling robot. Undertake co-crystallization of polymerase domain with primer and template DNA oligomers
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| January 2009 | Godfree Mlambo
Development of an Animal Model for Pre-clinical Evaluation of Plasmodium falciparum Transmission-blocking Vaccine (Pfs48/45) Using Transgenic P. berghei Parasites Aims
1. To make transgenic P. berghei parasites expressing the P. falciparum sexual antigen Pfs48/45 2. To evaluate sera from non-human primates immunized with the Pfs48/45 vaccine 3. To test whether natural infection with the transgenic parasite boosts antibodies to the antigen Pfs48/45 4. To understand fertilization receptor functional conservation between P. berghei and P. falciparum |
| Jayme Souza-Neto
The Generation and Characterization of Immune Pathway Inducible Plasmodium Resistant Transgenic Mosquitoes Aims
1. Generate an inducible Rel2 construct for the generation of transgenic A. stephensi mosquitoes 2. Characterize the dox-dependent rtTa-driven induction of the Rel2 factor 3. Characterize the dox-induced Rel2 mediated resistance to Plasmodium infection at the ookinete stage 4. Assess the impact of dox-mediated Rel2 activation on mosquito longevity and fecundity |
| Gundula Bosch
Structural and Functional of Iron-Sulfur Proteins in Isoprenoid Biosynthesis and Utilization in Plasmodium falciparum Aims
1. To produce and characterize the IspG, IspH and MiaB enzymes 2. To reveal the active site architecture and catalytic mechanism of IspG, IspH and MiaB
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| January 2010 | Grant Hughes
Introduction of Wolbachia into Anopheles gambiae and Modulation of Plasmodium Vector Competence Aims
1. Artificially trans-infect Anopheles gambiae with Wolbachia. Trans-infections will be performed with two strains of Wolbachia (wMelPop and wAlbB), which have been pre-adapted to Anopheles in cell culture 2. Characterize the novel Wolbachia-Anopheles association. Transmission rates, life-shortening and reproductive manipulations on the host will be assessed in the mosquito. Additionally, the distribution of Wolbachia within the mosquito will be characterized. Anopheles gene expression in response to Wolbachia infection will be analyzed in whole mosquitoes by microarrays 3. Determine Wolbachia-Plasmodium interactions. Wolbachia infected mosquitoes will be challenged with Plasmodium and development of the parasite analyzed to determine if Wolbachia interferes with parasite development and transmission
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| January 2011 | Jennifer Armistead
Mechanism of action of a mosquito-based malaria transmission-blocking vaccine
Aims
1. Characterize the APN1-ookinete molecular interaction
2. Identify protective epitopes of the NT135APN1 fragment |
| Jolyn Gisselberg
Iron Sulfur Cluster Synthesis in the Apicoplast of Plasmodium falciparum
Aims
1. Determine the subcellular location and activity of Suf pathway proteins
2. Probe the essentiality of the Suf pathway using reverse genetic approaches
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| January 2012 | Adelaide (Ulli) Hain
Targeting Atg8 and its essential interactions in the malaria parasite
Aims
1. Characterize Plasmodium Atg8's role in autophagy
2. Identify novel functions of Atg8 in Plasmodium
3. Develop specific inhibitors against Atg8 and its crucial interactions |
| Renato deFreitas
Pharmacokinetic Optimization of Plasmepsin Inhibitors
Aims
1. To identify the inhibitors with the most favorable cellular efficacy for further pharmacokinetic studies, including microsomal stability, permeability, bioavailability and toxicity
2. To perform toxicity studies in mice and rats and to perform efficacy studies in humanized mice model that can be infected by P. falciparum
3. To use animal results to build a QSAR model in order to find a correlation between the structure, pharmacokinetic and efficacy parameters of the inhibitors
4. Application of the QSAR models to design new compounds with better efficacy in animals and potentially in humans
5. To generate the appropriate data to begin a Phase 0 study in humans
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| 2003 | Ravi Dhar, PhD
Dr. Dhar is a scientist with the National Institute of Immunology, New Delhi, India. He spent five months in the laboratory of Nirbhay Kumar, learning advanced molecular techniques for genotype analysis of Plasmodium falciparum in India. With the knowledge he gained during his fellowship, he will study parasite diversity in severe and non-severe infections in Indian patients, apply this information to the study of responses to antimalarial drugs and build bridges for future collaboration with JHMRI investigators. |
| 2006 | Moonga Hawela, Msc
Mr. Hawela is a Biomedical Scientist and Acting Chief Parasitologist with the National Malaria Control Centre in Zambia. He spent three months in the laboratory of Dr. David Sullivan where he mastered the techniques of extraction of parasite DNA, amplification of MSP2 for P. falciparum, trained to use MSP2 primers and received extensive training in performance of electrophoresis and reading of gels. |
| 2007 | Luciano Moreira, PhD
Dr. Moreira is an Associate Researcher with the Malaria Laboratory of Centro de Pesquisas Rene Rachou/FIOCRUZ, Brazil. He spent 1 month in the laboratory of Dr. Marcelo Jacobs-Lorena learning Plasmodium falciparum culture and mosquito transmission techniques. |
| 2008 | Ruth Nyakundi, Msc
Ms. Nyakundi is an Assistant Research Scientist with the Department of Tropical and Infectious Diseases, Institute of Primate Research in Nairobi, Kenya. She spent 3 months in the laboratory of Dr. Nirbhay Kumar, to gain expertise in P. falciparum culture and mosquito transmission methods to introduce her and her institution to new technology and new techniques. |
| 2009 | Panadda Krairojananan, MS
Ms. Krairojanan is a PhD candidate and Assistant Chief with the Molecular Biology Section, Department of Entomology for the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand. She spent 3 months in the laboratory of Dr. Rhoel Dinglasan studying the molecular mechanisms of Plasmodium-mosquito interactions. The experiences she gained not only benefited her but her Institution in molecular techniques as much of these techniques were not available at the Mahidol University and AFRIMS. |
| 2011 | Santosh Anand Sripada, PhD
Dr. Sripada is a PhD student at the University of Hyderabad, Department of Biotechnology, School of Life Sciences in India. Spent 3 months in the laboratory of Dr. Isabelle Coppens studying the liver stages of Plasmodium understanding the hepatocyte-sporozoite interactions and developing novel therapeutic interventions. |
