Jayabalasingham, B
Kent, Rebekah
LeBlanc, Ralph
Noland, Greg
Ruben, Adam

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

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 

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

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

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

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

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 intraheptic parasites

2.  Functional analysis of the role Plasmodium ABCG1 transporter homologues in parasite cholesterol homeostasis

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.