Explore Awarded Grants

By using strips of mosquito netting around houses to turn the homes into mosquito traps, Jacques Derek Charlwood of Denmarks DBL Center for Health Research and Development, in conjunction with the INS of Mozambique, hopes to develop a simple new technique to reduce malaria transmission.

Elijah Songok at the Kenya Medical Research Institute hopes to better understand preliminary findings from studies of sex workers that natural resistance to HIV may be linked to genetic markers for type 2 diabetes.

Marilia Cascalho of the University of Michigan will test whether a "mutable"DNA vaccine in which the gene coding for the antigen mutates a million times more frequently than a typical gene will trigger immune response that anticipates the production of new viral variants and produces broadly neutralizing antibodies against HIV.

Ellen Vitetta of University of Texas Southwestern Medical Center at Dallas is developing a new vaccine platform that will utilize synthetic B cell epitope mimetics (peptoids) conjugated to protein carriers to make vaccines that will induce robust, specific, and protective antibody responses against pathogens.

George O'Toole, a microbiologist at Darmouth Medical School, and Mark Grinstaff, a biomedical engineer and chemist at Boston University, will work to develop an expansile nanoparticle, packed with high concentrations of antibiotics, which would expand and release their content when internalized by host cells. The hope is that more precise delivery of high concentrations of antimicrobial agents, in single or combination therapies, will reduce the development of resistance.

People born with a natural resistance to the HIV virus have a genetic mutation in the CCR5 gene. Karthikeyan Kandavelou of Pondicherry Biotech Pvt. Ltd. in India will attempt to achieve targeted disruption of CCR5 genes, making an important first step in a new strategy to make people permanently resistant to HIV.

Dr. Ryan Lilien of the University of Toronto in Canada will work to computationally model the structural and functional effects of point mutations on a target protein's active site. With the development of predictive models of pathogen evolution and the spread of resistance, this information can be used to guide drug development and optimization.

HIV has a very high rate of mutation allowing it to very rapidly develop resistance to AIDS therapies. The essential viral enzyme, HIV reverse transcriptase, lacks a "proofreading" or "repair activity" leading to errors or mutations. Karen Anderson of Yale University is working on "stealth" compounds that have a unique anchor specific for HIV. These compounds encourage the virus to make mutations until the virus is annihilated.

Olaf Kutsch of the University of Alabama proposes that HIV latency is controlled by host-gene promoter interference, a mechanism that prevents the initiation of viral gene expression. Understanding how host-gene promoter interference controls latent HIV-1 infection may aid development of therapies to deplete latent HIV in patients.

Yue Chen of the University of Pittsburgh will attempt to develop an oral HIV vaccine based on Clostridium perfringens, a bacteria able to withstand upper GI conditions to deliver large amounts of antigens to gut-associated lymphoid tissue, a major site of HIV activity.

Xilin Zhao of the University of Medicine and Dentistry of New Jersey will test whether anaerobic gas, which causes rapid depletion of oxygen, will kill the tuberculosis bacteria without permanent damage to surrounding tissue.

A3G, protein found in human cells that inactivates several viruses including HIV, is "switched off" in proliferating T cells. Harold Smith of the University of Rochester will screen for small molecule compounds that bind to A3G in cells and turn its anti-viral activity back on.

To test the hypothesis that immunization with a non-HIV antigen will neutralize the virus, Jinhua Xiang of the University of Iowa will determine if immunization with an envelope protein of the GB Virus C elicits antibodies that block HIV replication.

Pandelakis Koni of the Medical College of Georgia will study the complex sugar coating that surrounds and protects HIV to see if parts of this shield can serve as targets for a vaccine, to generate antibodies that bind to and accelerate the killing of HIV-infected cells.

Francis Nano of Canada's University of Victoria will introduce essential genes found in Arctic bacteria into the genomes of "warm-loving" pathogens, making them unable to grow at core body temperatures. Such microbes could survive on human skin, which is cold enough to allow for replication and the stimulation of a strong immune system response, but not survive further dissemination into deeper and warmer tissue.

Benjamin Chain of University College London will attempt to stimulate an antibody response against CCR5, a protein found in the body which is used by HIV to infect cells. By combining a small portion of the molecule with part of the tetanus bacterium, Chain hopes to overcome natural tolerance of CCR5 to deplete the presence of the protein and prevent a way for HIV to enter cells.

Vojo Deretic of the University of New Mexico in the U.S. proposed that autophagy, a process by which cells destroy cellular components and intracellular pathogens, can be induced through drug therapy to not only destroy the HIV virus in infected cells, but also to block its transmission from dendritic cells to T cells. This project's Phase I research demonstrated that autophagy can destroy HIV, block dendritic to T cell transfer of HIV, and promote antigen presentation by dendritic cells. In Phase II, Deretic's team will screen for compounds that can induce autophagy to block HIV from infecting cells, limit HIV spread, and enhance dendritic cell immune functions.

To interrupt reproduction of the malaria parasite in the mosquito gut, Greg Garcia and Sheetij Dutta of Walter Reed Army Institute of Research seek to identify and block a gametocyte stage receptor for xanthreunic acid, which is known to trigger the differentiation of gametocytes, an essential step in the life-cycle of the malaria parasite.

Sarah Fortune of Harvard University will research whether chromatin crystallization, in which DNA condenses into a protective matrix due to environmental stress, occurs in tuberculosis and is a characteristic of latent organisms.

John Altman of Emory University in the U.S. will research whether a drug which induces lymphopenia and is currently in clinical trials can effectively reduce T-cell exhaustion and induce immune-mediated clearance of the SIV infection.

Abraham Pinter of the University of Medicine and Dentistry of New Jersey will study the mechanisms that make neutralizing epitopes within conserved sites of the HIV virus resistant to antibodies, and will screen for reagents that can "unmask" these epitopes so that antibodies can target and eliminate the virus.

Andrew Heath of University of Sheffield in the U.K. will research whether the immune responses to DNA vaccines can be enhanced with novel adjuvants.

Odile Ouwe Missi Oukem of Cameroon's Centre International de Reference Chantal Biya will set up a suite of computer tools to manage and analyze biological, clinical and epidemiological data collected from African HIV-infected patients to better study HIV resistance to antiretroviral drugs.

Because a robust immune response can actually foster HIV replication and spread, Joseph (Mike) McCune at the University of California at San Francisco in the U.S. proposed that building tolerance to HIV will hinder disease progression better than vaccinations that activate the immune system and trigger HIV activity. This project's Phase I research demonstrated in a non-human primate model that tolerance to SIV could be induced by introducing SIV antigens to fetuses in utero. In Phase II, McCune and colleagues will work to optimize this approach by identifying which antigens best confer this "protective immunity," and testing whether and how long this protection lasts after birth.

Barry Peters of Kings College London will study the balance of tolerizing and stimulating immunity in HIV patients identified as "long-term non-progressors" in an effort to determine whether it is development of tolerance to HIV, and not immunity, which prevents the progression of the disease to AIDS.

The bacteria Bdellovibrio -- harmless to humans -- naturally kill a wide range of gram-negative pathogens which are known to cause many infections. Professor Liz Sockett of the University of Nottingham in England will study whether these pathogens have the ability to form resistance to Bdellovibrio, and if Bdellovibrio can be delivered to patients as a living antibiotic.

Hugo Soudeyns of Canada's Centre de Recherche du CHU Sainte-Justine will incorporate engineered frameshifting gene cassettes into vaccine vectors in hopes of eliciting broader T helper and cytotoxic T cell response, leading to better protection against disease.

Using thermostable nanoparticles as a delivery mechanism, Yasmin Thanavala of Health Research Inc and Roswell Park Cancer Institute in the U.S. will work to develop a single dose vaccine that can be given as close to birth as possible to protect against multiple diseases.

Type III protein secretion systems are used by many bacteria to inject proteins into mammalian cells. Jorge Galan of Yale University will develop an antigen delivery machine based on the type III protein delivery system that will not require the use of live-attenuated bacteria, offering a safer vaccine platform.

Roy Kishony of Harvard University will seek to identify chemical entities that act as "selection inverters" which actively target antibiotic-resistant bacteria. Selection- inverters could be used in combination with traditional antibiotics to prevent resistance and possibly even drive a drug-resistant bacteria population back to drug sensitivity.

Timothy Geary at McGill University in Canada proposed screening chemicals derived from the biological diversity found in Africa to identify lead compounds for the development of drugs to treat infections caused by parasitic nematode worms. In this project's Phase I research, Dr. Geary established drug discovery centers at the Universities of Botswana and Cape Town, South Africa to screen for compounds that target a nematode family of peptidergic G Protein-coupled receptors. In Phase II, the team is expanding the screening efforts.

Nur Alam of the International Centre for Diarrhoeal Disease Research, Bangladesh will test whether adding L-isoleucine and Vitamin D to food served to hospitalized children will induce secretion of antimicrobial peptides that can aid recovery from acute diarrhea and pneumonia.

Ralph Albrecht of the University of Wisconsin in the U.S. seeks to develop magnetite nanoparticles conjugated to antibodies that will selectively bind to HIV-infected cells. Once bound to the infected cells, the magnetite is heated using an externally applied magnetic field; melting holes in the membrane of the infected cell and killing it.

Brian Foy and Massamba Sylla of Colorado State University will research whether providing endectocides, drugs that kill parasitic worms, to animals and humans will effectively kill mosquitoes which feed on them. Through targeted and spaced drug administration, mosquitoes incubating disease-causing pathogens are expected to die prematurely, thus interrupting disease transmission, but these methods would limit the development of endectocide resistance.

Nikita Malavia of Boston's Children's Hospital has teamed up with MIT's Robert Langer to engineer nanoparticles that mimic host cells in an attempt to deceive viruses into releasing genetic material which is rendered useless by viral inhibitors.

Marilyn Fernandez of Altor Bioscience Corporation in the U.S. will engineer single chain T cell receptors (TCR) to deliver immunotherapies to HIV-infected cells. These TCRs will be engineered to recognize known viral variants to linked to the emergence of drug-resistant HIV mutations.

Samuel Landry of Tulane University will research the use of immune tolerance of dominant HIV epitopes prior to conventional vaccination with an HIV protein in order to stimulate a broader immune response.

Irina Caminschi of the Walter and Eliza Hall Institute of Medical Research in Australia will test whether a prototype malaria vaccine which targets a newly identified dendritic cell molecule will produce a strong antibody response without the use of adjuvants.

Johnny He of Indiana University proposes to engineer biodegradable nanoparticles that target active and latent HIV-infected cells by binding to the carbohydrate portion of the protein gp120, which the virus uses to seek out host cells. The "sticky" nanoparticles would then bind HIV, either in the blood, or within cells, killing the virus.

While humans and chimpanzees share an overwhelming similarity between genes, primates exhibit a resistance to AIDS. Walter Messier of biotechnology company Evolutionary Genomics in the U.S. will research the mechanisms of eight genes that have adapted in chimps to identify how viral suppression works.

Lactobacillus bacteria, typically found in the cervix and vagina of healthy women, have been found to provide a natural barrier against HIV infection. Dr. Leonard Damelin will investigate whether anti-HIV molecules can be introduced via bacteriophages into existing Lactobacillus populations to further fortify this protective barrier.

Tayyaba Hasan of Harvard University in the U.S. will work to design a conjugate which will attach to the GP63 enzyme of the Leishmania parasite. This therapy will consist of a lightactivatable, non-toxic chemical that will be activated by a light source, killing the parasite but leaving surrounding cells intact.

Samantha Sampson of Imperial College London proposes introducing short strands of modified DNA into tuberculosis cells for direct and highly specific targeting of DNA sequences. If successful, it will effectively "lock" DNA, obstruct replication and transcription, and prevent bacterial growth and survival.

Manipulation of skin cells can now create pluripotent cells which can proliferate and differentiate into many human cell types. This new technology will be employed by Jeanne Loring of the Burnham Institute for Medical Research to generate pluripotent cell lines for ethnically diverse populations to be used a genetically appropriate model to develop more specific and appropriate therapies against infectious disease.

Allan Saul of the Novartis Vaccines Institute for Global Health in Italy will genetically modify gram-negative bacteria to generate large quantities of their outer membranes, which can be loaded with antigens that stimulate immune responses. This technology could prove to be a reliable and economic platform for generation of new vaccines.

Using genome scans, Alfred Roca of the University of Illinois will test the possibility that isolated African populations have been repeatedly exposed to chimpanzee immunodeficiency viruses, and have evolved resistance to HIV. Ascertaining whether they display resistance to HIV could lead to new ways to fight HIV in other populations.

Saurabh Gupta and Ron Weiss of Massachusetts Institute of Technology in the U.S. proposed creating sentinel cells that can detect the presence of a pathogen, report its identity with a biological signal, and secrete molecules to destroy it. This project's Phase I research demonstrated that commensal bacteria can be engineered to detect and specifically kill the model bacterial pathogen Pseudomonas aeruginosa. In Phase II, Gupta and Weiss will engineer the human microbiota to specifically detect and destroy the gut pathogen Shigella flexneri, which is responsible for high mortality rates in children.

Christina Smolke proposes to develop synthetic RNA devices that can process and transmit molecular input signals in hopes that this technology will result in more effective, targeted strategies for detecting and protecting against infectious disease.

Matyas Sandor of the University of Wisconsin will graft granulomas, nodules that form as a result of long-term inflammation, to study the role they play in TB latency and reactivation.

Huan Nguyen of the International Vaccine Institute in Korea will explore whether green fluorescent protein is endowed with unique immunological properties which could be used to develop a universal flu vaccine.

Keith Jerome of the University of Washington in the U.S. will utilize a class of proteins called homing endonucleases, which have the ability to cut DNA sequences, to target the DNA sequences unique to HIV, thus disabling the virus from making any more copies of itself. This project's Phase I research demonstrated that homing endonucleases can find a model virus hidden in the genes of infected cells. In Phase II, Jerome's team is now modifying these proteins in hopes of producing several that can specifically target and destroy HIV within infected cells.

Alexandre Alcais of French National Institute for Health and Medical Research will study whether there is a genetic basis for innate resistance to TB infection through genome-wide linkage analysis of TB-specific T-cell phenotypes.

Pattamaporn Kittayapong of Mahidol University in Thailand will study how Wolbachia, a symbiotic bacteria which infects many species of insects, may to limit dengue virus infection in mosquitoes.

HIV uses protein interaction pathways to force host cells to make more HIV copies. Judith Klein of Carnegie Mellon University aims to use advanced computational methods to predict parallel pathways that can be found and used to circumvent the points of HIV interception.

With evidence that RNA interference is a component of virus infection resistance, Andrew Fire of Stanford University will seek to understand how RNAi can function as a natural antiviral mechanism, and how such analysis can enable the design of antiviral interventions.

Dirk Linke of the Max Planck Society in Germany seeks to identify and classify all the molecules that make up the cell wall of gram-negative bacteria, which causes a major portion of infectious diseases. By recognizing common elements among these molecules, a broad-range vaccine could be developed to protect against a number of these diseases.

Douglas Nixon of the University of California at San Francisco will test his hypothesis that APOBEC proteins, which have been found to restrict replication of HIV, can be used to as an immunogen to stimulate a T cell response which would act against HIV infected cells.

Humberto Lanz-Mendoza of Mexico's Instituto Nacional de Salud Publica will test whether mosquitoes can become resistant to dengue and malaria by the introduction of non-virulent pathogens, which might stimulate immune priming and protect against subsequent infections.

With a team of researchers, economists and physician-scientists, Matthew Davis of the University of Michigan will establish a program to link new vaccine discoveries with vaccine manufacturers in developing countries while simultaneously evaluating ways to help these manufacturers purchase rights to these innovative candidates.

Pulmonary macrophages are the principal host of tuberculosis, where it can remain latent and inaccessible to current TB drug therapies. Dmitry Shayakhmetov of the University of Washington will study whether infecting these host cells with adenovirus will induce rapid cell death, reducing TB load and blocking the re-infection cycle.

Amelia Crampin of the London School of Hygiene & Tropical Medicine will study a group of people found to have latent tuberculosis in the 1980s to test her hypothesis that a measurable portion of them have cleared the infection spontaneously. Proof that some people can clear infection opens the door for research to discover how this works.

Anthony Mbonye of the Tropical Disease Research Network in Uganda will assess the feasibility and effectiveness of using private sector midwives to provide HIV testing and antiretroviral drugs in an effort to reduce mother to child transmission of HIV.

Barbara Kazmierczak of Yale University will test whether changes in the bacteria that naturally reside in human bowels affect vaccine responsiveness.

Joseph DeRisi of the University of California at San Francisco proposes to engineer naturally occurring erythrotropic bacteria to target malaria infected red blood cells to serve as a potential prophylactic and treatment for malaria in humans.

Philip Bryan of the University of Maryland will use an engineered protease to destroy a specific Plasmodium surface protein that is essential in host cell invasion.

Dr. Yen Wah Tong of the National University of Singapore will attempt to fabricate nanoscale, imprinted particles that can capture viruses, effectively preventing them from infecting cells. These non-toxic and biocompatible polymers can then be excreted from the body. This synthetic equivalent to natural antibodies would eliminate the need for a human immune response and resulting mutations of the virus' DNA.

Shi-hua Xiang of the Dana Farber Cancer Institute in the U.S. proposed engineering Lactobacillus, bacteria which normally reside in the human genital and gastrointestinal tract, to carry anti-HIV agents such as neutralizing antibodies, peptides, or other inhibitors. He and his colleagues hypothesized that introducing the engineered bacteria into the gastrointestinal tract would allow the bacteria to colonize and provide long-lasting protection against the virus. This project's Phase I research demonstrated that the engineered anti-HIV Lactobacillus can efficiently block HIV infection in a tissue culture system. In Phase II, Xiang (now at the University of Nebraska) and colleagues are testing this approach in a non-human primate model.

Mark Davis of Stanford University in the U.S. will develop a new method to assess specific T cell responses to vaccinations. Using combinations of labeled tetramers to identify many types of T cell responses, Davis hopes to create better and more comprehensive assessments of immunity generated by vaccines. This project's Phase I led to the development of a new way to color-code T cells as a way to visually quantify immune response to an influenza vaccine. In Phase II, Davis and his team are extending this approach to quantify immune response to other vaccines in an effort to reduce the time needed to determine if a vaccine is working.

Graham Rook of University College London will target an essential bacterial nutrient transport system with an iron-binding nanoparticle. The particle will be designed not only to block the pore and prevent it from taking in needed nutrients, but to also carry antibiotics that can be released in the vicinity of the bacterium.

Anwar Jardine of the University of Cape Town in South Africa will attempt to disrupt the biosynthetic pathway of mycothiol, which is produced by the tuberculosis bacterium as a protective chemical compound. By targeting this metabolic pathway specific to mycobacteria, Jardine hopes to eliminate latent tuberculosis or make it more vulnerable to existing drugs.

Dan Feldheim of the University of Colorado in the U.S. will test his hypothesis that gold nanocrystals coated with drug compounds can effectively inhibit protein- protein interactions that often drive disease pathogenesis, will be less susceptible to evolutionary mechanisms that lead to drug resistance, and offer enhanced drug delivery characteristics. This project's Phase I research demonstrated that gold nanocrystals can be tailored to circumvent many viral and bacterial evolutionary drug resistance mechanisms. In Phase II, he is now studying the ability of small molecule-coated nanoparticles to withstand resistance mechanisms of Mycobacterium tuberculosis (TB).

Mark Kendall of the University of Queensland in Australia will design and test nanopatches, small patches consisting of microscopic silicon projections coated with a malaria vaccine in dry form, to target immunologically-sensitive cells within the skin's outer layers - that are missed by the needle and syringe - to induce unique and protective immune response against the disease.

CPS conjugated vaccines, such as those used to combat pneumonia, are difficult and expensive to produce. George Wang of Ohio State University will use bacteria engineered to express CPS, the carrier protein and a key enzyme which will bind the two together in an effort to develop a simpler and more economically feasible method of vaccine production.

Hiroshi Kiyono of the University of Tokyo will work to advance a rice-based oral vaccine that can induce both mucosal and systemic immunity. If successful, the MucoRice system can be self-administered and will not require syringes or refrigeration.

Volker Gerdts of Canada's Vaccine and Infectious Disease Organization proposes to use live viral vectors to immunize fetuses during pregnancy to induce immune responses in the unborn baby, thereby protecting the infant against early life infections.

To generate the large numbers of infective malaria sporozites needed for use in an effective vaccine, James Kublin of the Fred Hutchinson Cancer Research Center in the U.S. will use high throughput screens to develop a library of media compounds needed to optimize in vitro production.

Stephen Johnston of Arizona State University will investigate whether HIV causes deficient protein synthesis in infected cells. This knowledge could be used to stimulate normal human T cells to destroy infected cells based on these aberrant host antigens.

In pursuit of a new type of AIDS vaccine, Zhiwei Chen of the University of Hong Kong will work to use a variant of the primate CCR5 gene as an antigen and test its efficacy in inducing cross-neutralizing antibodies against this important HIV co-receptor.

Optical information, temperature gradients, trace gases and volatile odors are key sensory inputs for mosquitoes. To mitigate the transmission of malaria, Szabolcs Marka of Columbia University in the U.S. will research how optical irradiation might be used to physically disrupt mosquitoes' sensory systems such that they can't find human hosts. This project's Phase I research demonstrated that insects are repelled or change their flight behavior in response to different infrared light gradients. In Phase II, Marka's team will build on this research to design a prototype device that can deter insect vectors from human hosts.

Jay Solnick of the University of California, Davis will explore whether the bacteria Helicobacter pylori, which can cause peptic ulcers in some people, might enhance immunity to tuberculosis and help maintain tuberculosis in a latent state.

Professor Hiroyuki Matsuoka of Jichi Medical University in Japan will attempt to design a mosquito that can produce and secrete a malaria vaccine protein into a host's skin. The hope is that such mosquitoes could deliver protective vaccines against other infectious diseases as well.

To test the theory neutralizing antibodies can be "programmed" to recognize broadly divergent HIV envelope proteins, Nancy Haigwood of Oregon Health & Science University will work to design components of an HIV vaccine using groups of related envelope sequences.

Dennis Hartigan-O'Connor of the University of California at San Francisco in the U.S. will test whether expanding Th17 cell populations, a subset of CD4 T cells that protect the gastrointestinal tract against microbes, can augment the gut's general defenses and protect against the acute and chronic effects of HIV. In this project's Phase I research, Hartigan-O'Connor and colleagues tested this hypothesis in macaques and found that the Th17 population present before SIV infection has a lasting impact on the course of disease and that natural variability in Th17 populations might partly account for variability in control of SIV infection. In Phase II, the team will test the idea that an oral drug can be used to pharmacologically manipulate Th17 populations in vivo in young macaques, the goal being enhanced control of retroviral replication.

Because cystic fibrosis patients and carriers appear to be resistant to tuberculosis, Jerry Nick of National Jewish Medical and Research Center in the U.S. will study whether mutations of the CFTR gene, which causes the disease, reduce or eliminate latent TB infection.

Brendan Wren of the London School of Hygiene & Tropical Medicine in the UK will test a new bacterial synthesis method, Protein Glycan Coupling Technology. This method uses bacteria to attach proteins to glycans to produce glycoconjugate vaccines, and it could lead to an improved vaccine against pneumococcal disease. This project's Phase I research demonstrated that a Streptococcus pneumoniae capsular polysaccharide could be transferred to a carrier protein in E. coli. In Phase II, this research will be extended to further capsular determinants with the goal of producing a broad coverage, inexpensive pneumococcal vaccine.

Teun Bousema of Radboud University in the Netherlands proposed that geographic "hotspots" of malaria disease drive local transmission, and therefore that interventions would most efficiently be deployed if they targeted these hotspots. This project's Phase I research demonstrated that hotspots of malaria transmission are present at all levels of endemicity and can be sensitively detected by serological markers of malaria exposure. In Phase II, Bousema and colleagues will define hotspots of malaria transmission in Africa in a site of moderate endemicity in Mali and in the low endemicity highlands in Kenya. Once hotspots are detected, they will be targeted with a combination of those interventions deemed most efficacious based on a mathematical simulation, the goal being to locally interrupt malaria transmission.

Jord Stam at Utrecht University in the Netherlands will attempt to create "two-sided" antibodies to fight HIV; one side would attach to HIV, and the other side would safely deposit the virus in cells in which it cannot replicate.

In an effort to enhance pathogen vulnerability to existing antibiotics, Angharad Davies of Swansea University in the U.K. proposes using peptides which activate stationary-phase microbes, leading to cell growth, with the aim of increasing susceptibility to established treatments.

Ron Raines of the University of Wisconsin proposes to convert a ribonuclease that rapidly degrades RNA into a zymogen, an enzyme precursor that is activated only when cleaved by an HIV protease. Because this cleaving can only occur within HIV-infected cells, the toxic activity of the ribonuclease will be unleashed only in cells in which HIV is active.

Carl Nathan, Julien Vaubourgeix and Gang Lin of Weill Cornell Medical College will test their hypothesis that tuberculosis is able to exit latency by distributing damaged proteins to a senescent cell lineage, while more functional proteins are diverted to a lineage with full replication potential. Regulating this post-latency cell division could be the target of new drugs. This project's Phase I research demonstrated that M. tuberculosis accumulates irreversibly oxidized proteins when its replication is blocked. These proteins form small aggregates that fuse into larger ones. One member of the progeny pair retains the aggregates when cell division resumes. In Phase II, the team will work to identify the genes that control this process for use in screens to find new and more powerful TB therapies.

Eduardo Trombetta of New York University will study whether reducing the ability of lysomes to digest protein antigens in vaccines could enhance the vaccine's ability to elicit antibody and T cell responses.

Dan Kaufman of the University of Minnesota will test whether natural killer cells, generated from stem cells can effectively target and eliminate HIV-infected cells.

To fight emergence of drug and vaccine resistance in rapidly evolving parasites, Pradipsinh K. Rathod of the University of Washington in the U.S. will identify the parts of the malaria genome which contribute to rapid increases in mutations, and will screen for small molecules that inhibit these mechanisms. This project's Phase I research demonstrated that hypermutagenesis does play a strong role in the development of drug resistance. In Phase II, Rathod's team is continuing to isolate the genetic drivers of hypermutagenesis with the aim of developing a way to disable the process and improve success rates of anti-malarial drugs.

Employing new high throughput methods, antibiotic screening technologies and rapid genomic sequencing methods, George Church of Harvard University will partner with labs in South Africa to develop a new approach to identifying, studying, and limiting emerging drug resistance.

Olen Kew of the Centers for Disease Control and Prevention in the U.S. will attempt to develop a safe and effective polio strain for use in an inactivated vaccine by modifying codon usage patterns in polio strains to control viral mutation rates, lower infectivity, and raise genetic stability.

In an attempt to capture and study latent tuberculosis cells, which are reservoirs of infection and highly resistant to treatment, Kim Lewis of Northeastern University will pulse-label tuberculosis cells with green fluorescent protein. While active cells divide and dilute the GFP, latent cells, which are dormant, will remain bright green, allowing for their observation and tracking.

Ali Munawar of Molecmo Nanobiotechnologies in the U.S. aims to identify the specific protein that enables the HIV virus to access various sites within the host cell for replication. Identification of this protein will advance the development of a novel class of small molecule inhibitors that disrupt the HIV life cycle.

Ms. Sanah Jowhari at TheraCarb, a biotechnology company in Canada, will apply polymer-based drug technology to capture and remove the Cholera toxin from the body of a host, and validate an approach to developing a viable drug candidate for Cholera.

Suzanne Fleiszig of the University of California, Berkeley will attempt to decipher the molecular mechanisms that maintain broad-spectrum antimicrobial activity of the healthy eye, which could lead to innovative strategies to combat infectious disease in general.

To provoke an effective immune response against HIV, George Dickson of Royal Holloway -University of London will utilize HIV-based lentivectors encoded with a strong neutralizing epitope derived from tetanus toxin or influenza on its surface. By forcing production of such highly immunogenic and stable antigens, the immune system will respond with corresponding antibodies and control virus replication.