Explore Awarded Grants

Xiao-Guang Chen, Zetian Lai and Chunmei Wang of Southern Medical University in China and their international partner Guiyun Yan of the University of California, Irvine in the U.S. will develop new traps that are more attractive to malaria vectors. They will incorporate the new traps with infrared vector detection, automatic recording and wireless transmission technologies, and test the efficacy of the new trap and the automated malaria vector surveillance apparatus both in the laboratory and in the field. This novel, real-time malaria vector surveillance tool can help efficiently monitor biting behavior, population abundance and transmission dynamics of malaria vectors, and tremendously enhance malaria transmission surveillance and facilitate the evaluation of new vector control measures targeting outdoor malaria vectors.

Zhang Dongjing, Zheng Xiaoying, Wu Yu and Wang Gang of Sun Yat-sen University in China together with their international partners Badria El-Sayed, Tellal Ageep, Ammar Hassan and Mohamed Korti all from the National Centre for Research in Sudan, and Jeremy Bouyer, Maiga Hamidou, Hanano Yamada and Adly Abdalla of Insect Pest Control Laboratory in Austria will develop highly specific and environmentally friendly Sterile Insect Technique (SIT) to control outdoor Anopheles mosquitoes. Once the feasibility evaluation is passed, the results will form a systematic technical package of SIT to control Anopheles stephensi and provide the scientific basis and technical support for subsequent field trials of SIT to control this outdoor malaria vector in African countries such as Sudan or other Asian countries.

Weiguo Fang of Zhejiang University and Guoding Zhu of Jiangsu Institute of Parasitic Diseases in China together with their international partner Abdoulaye Diabaté of Institut de Recherche en Sciences de La Santé in Burkina Faso, by referring to the widely used small farmer-operated factories for production of entomopathogenic fungal spores in China, will develop a spore production technology for the transgenic Metarhizium strain, which is cost-effective, of low technological bar and can be easily implemented in low-and middle-income countries and regions. A novel bifunctional device will also be provided for outdoor mosquito control. Currently, mycoinsecticides and their release devices are only suitable for indoor mosquito control.

GuoXiong Peng, Yuxian Xia, Yueqing Cao and ZhengBo He of Chongqing University in China together with their international partner Raymond J. St. Leger of the University of Maryland in the U.S. will screen mosquitocidal fungal strains from China and abroad for high-yield virulent and stable production strains against larvae and adults, test the safety of the production strains, optimize solid fermentation medium, fermentation process and the components and proportion in the formulation to develop oil-based fungal mosquitocides for outdoor application. This will help address issues including mosquito resistance and environmental pollution caused by massive use of chemical insecticides.

Biao Jiang, Jianhua Yao, Ping Xing, Jia Li and Wanjun Wang of the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences together with their international partners Ole Skovmand and Sérgio Sousa both of Landcent (Europe) B.V. in The Netherlands will utilize in silico screening to discover mosquito insecticide or repellent compounds in traditional Chinese medicine. At least one safe, environmentally friendly and efficient novel mosquito insecticide or repellent insecticide is expected to be obtained, which will then be used to further develop outdoor vector control technology or products. The development of such mosquito insecticides or repellent compounds will help address insecticide resistance issues and accelerate the global malaria elimination process.

Sibao Wang of the Institute for Biological Sciences, Chinese Academy of Sciences and Duoquan Wang from the China CDC together with their international partners Abdoulaye Diabaté of Institut de Recherche en Sciences de La Santé in Burkina Faso and Marcelo Jacobs-Lorena of Johns Hopkins University in the U.S. will develop procedures to efficiently introduce a specific bacterium into field mosquitoes in order to evaluate effectiveness of the bacterium spread through mosquito populations and to block parasite transmission in a more realistic setting. Introducing anti-Plasmodial symbiotic bacteria into mosquito populations can potentially transform mosquitoes into ineffective vectors. This unconventional approach has already shown promise in the laboratory.

Yilan Ye from Tsinghua University in China will develop a small, self-adhesive menstrual product based on the suction cups of octopuses that can be fixed securely but reversibly inside the vaginal opening to block the flow of blood and enable its convenient disposal. They will design it specifically for women and girls in low- and middle-income countries by ensuring it is low-cost, re-usable, safe to apply, and does not require sanitation facilities. They will experiment with different commercialized, biocompatible thermoplastic polyurethanes (TPUs) as the raw materials to produce the adhesive polymers. They will first test these polymers for their ability to be strongly, reversibly and repeatedly stuck to the surface of porcine livers and hearts as surrogates that mimic the moist and irregular skin surface inside the vagina. Finally, they will develop an inject mold to manufacture a prototype for human testing that also contains a soft valve for convenient release.

Xiaofan Liu at the City University of Hong Kong in China and colleagues will reconstruct COVID-19 transmission chains between individuals in communities and households using statistical methods applied to existing datasets to more reliably estimate COVID-19 transmission characteristics, such as reproduction rates, that are critical for planning effective control measures. Currently, transmission characteristics are estimated using aggregated-level data, which leads to inaccuracies. Ideally, data on how COVID-19 is transmitted between individuals are needed. They will curate an existing collection of datasets containing over 40,000 COVID-19 cases in five Asian countries with person-to-person transmission evidence to reconstruct transmission chains. They will then apply statistical tests and an analytical methodology called regression analysis to identify the most important transmission risk factors, which may include virus strain, transmission media, population density, and climate conditions.

Carol Sze Ki Lin of the City University of Hong Kong and Srinivas Mettu of the University of Melbourne in Australia will develop a new, low-cost bioreactor system to mimic the human gut and facilitate simultaneous growth of multiple bacterial strains with diverse growth requirements. A healthy mixture of bacteria in the human gut is essential to overall health, and live biotherapeutics could be used to restore this population in infants whose gut microbiota has been damaged by malnutrition. Manufacture of these therapeutics is difficult and expensive: the human gut contains multiple strains of bacteria with diverse environmental and nutritional growth requirements, and designing a bioreactor to accommodate such variation is difficult. They will create stratified growth zones within one reactor based on immobilization of the bacteria on a low-cost, biodegradable plant-based cellulose hydrogel. They will alter the porosity and surface chemistry of the hydrogel to create variations in pH and oxygen and nutrient levels within the reactor to simulate the human gut from stomach to rectum. This will facilitate the simultaneous growth of ten bacterial strains with diverse growth requirements, first in a lab setting and later on a commercial scale.

Linqi Zhang of Tsinghua University in China, working with Tongqing Zhou of the National Institutes of Health in the U.S., will design a broadly protective vaccine against HIV-1 derived from the atomic structure of the viral envelope protein from the dominant transmitted founder HIV-1 strain isolated from a high-risk population in China. HIV is a rapidly evolving virus that continually alters its structure to elude the immune system and antiretroviral drugs. This makes it challenging to develop an effective vaccine. The spike-shaped envelope protein complex of HIV extends from its surface to fuse with and infect human cells. Prior to cell fusion, this complex is folded into a closed conformation and is protected from immune cells by glycan molecules. They will use the known sequence and structure of the viral envelope protein to design and synthesize stabilized pre-fusion conformations that display accessible antibody binding sites that may make them more effective vaccines. The immunogenicity of these vaccines will be tested in small animal models and non-human primates.

Babak Javid of Tsinghua University in China, working with Paul MacAry of the National University of Singapore in Singapore, will study human monoclonal antibodies that protect individuals from infection by Mycobacterium tuberculosis and could be used to develop a tuberculosis vaccine. Tuberculosis is the world's most deadly infectious disease, and the causative bacteria are present in latent form in up to a quarter of the global population. They have discovered protective antibodies in three health care workers who are exposed to very high levels of Mycobacterium tuberculosis. They will isolate these antibodies from memory B cells to study how they bind to the bacteria and trigger a protective immune response. They will then develop an assay to screen larger numbers of workers to isolate and characterize more potent human antibodies that could be used to design an effective vaccine.

Lu Lu of Shanghai Medical College, Fudan University in China working with Ling Ye of Emory University in the U.S., will design a potent HIV vaccine using selected sequences of one of the virus's envelope proteins to trigger the production of broadly neutralizing antibodies. This has been problematic due to the diversity of the viral envelope glycoprotein and its glycosylation shield, which prevent the immune system from recognizing it. The membrane-proximal external region (MPER) of the viral envelope protein has been identified as an attractive target for inducing neutralizing antibodies, and they have fused it with another viral protein to form a chimera that can partly neutralize infection. They will build on this result by modifying the structure of the MPER to stabilize it in a more active conformation, and by fusing it with slightly different viral proteins that can then be immunized altogether. They will evaluate whether this vaccine strategy further stimulates broadly neutralizing antibody production and can fully neutralize HIV in several animal models.

Qian Gao of Shanghai Medical College Fudan University in China, working with Clif Barry of The National Institute of Allergy and Infectious Diseases in the U.S., will support a clinical trial to shorten the treatment time for tuberculosis (TB) from six months to four months by helping to identify predictive biomarkers in individuals that only require the shorter treatment. Shortening treatment when possible will substantially reduce costs and the emergence of drug resistance which is a major barrier to eradicating this deadly disease. The phase 2b clinical trial will recruit 620 TB patients at multiple clinics in South Africa and China who will be monitored for disease burden by PET/CT scans and diagnostic assays during treatment and will supply blood and sputum samples for testing. He will analyze RNA and inflammatory markers in serum samples from the Chinese trial participants to identify more robust biomarkers for predicting shorter treatments. He will also determine the strains of the causative Mycobacterium tuberculosis the source of any reinfection (relapse or new infection) and the presence of drug resistant bacteria in these patients and how these link with treatment duration and disease outcome.

Yang Cheng of Jiangnan University in China will develop a smartphone application to track Chinese individuals who move to work in other countries with high levels of malaria. When these migrant workers return home, there is a risk that they also import malaria, which can then be locally spread via mosquitoes and cause an outbreak. They will develop the application to measure body temperature and track location, and combine it with an existing malaria response system that is used to identify, track and treat malaria in the Jiangsu province, to improve the accuracy and speed of response.

Xun Suo of China Agricultural University in China will develop a rabbit model of cryptosporidiosis that mimics the human disease, which presents as severe diarrhea particularly in young children, to help identify new treatments. Current animal models of infection by the parasite Cryptosporidium are suboptimal: mice are not naturally infected, while pigs and calves can be infected but are expensive and more difficult to manage, and none show the same symptoms as humans. Rabbits are naturally infected by Cryptosporidium and display human-related symptoms. They are also practical to handle and breed, and are relatively inexpensive. They will isolate infective oocysts from diseased rabbits in the wild, and establish the infection in the laboratory. They will also devise protocols to evaluate the disease such as scoring the severity of symptoms, and sequencing the parasite strains. The value of their model as a screening platform for identifying new drugs will also be tested.

Gong Cheng of Tsinghua University in China will develop a glycan formula as a diet additive that specifically inhibits the lectin-based viral receptors in mosquitos, thereby providing a practical approach against dissemination of multiple mosquito-borne viruses.

Xu Tan of Tsinghua University in China will harness the genome-editing power of the CRISPR-Cas9 system to eliminate latent HIV infection and provide a proof-of-concept for a potential cure for HIV infection.

Qi Zhang of Tsinghua University in China will identify and characterize antibody germline precursors of broadly neutralizing monocolocal antibodies (bnmAbs) with the ultimate goal to design an HIV-1 vaccine candidate able to stimulate the precursors to develop into protective antibodies in healthy individuals.

Yu Rao of Tsinghua University in China will develop safe and potent covalent drugs (irreversible inhibitors) against multi-drug-resistant bacteria (MDR bacteria) and elucidate their molecular mechanisms with chemical probes.

Shan Feng of Tsinghua University in China will develop a novel reagent called DCAF to eliminate antibody-dependence-enhanced (ADE) Dengue virus infection. DCAF stands for Dual-functional Conjugate of Antigenic peptide and Fc-III tag, which is designed for the blocking of cross-reactive antibodies that can enhance secondary infection of Dengue virus. In the current phase, they will synthesize a group of DCAF molecules to test their binding affinities with the antibodies of Dengue virus 2 and to evaluate whether these molecules can be used to block the ADE process.

Xue Liu of Tsinghua University in China will identify antibacterial small molecules against the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) by screening compound libraries that contain compounds with novel chemical scaffolds. They will then use the identified antibacterials as probes to find new targets for antibiotic development. The current data include the discovery of two bacteriocidal compounds with novel scaffold structures.

Javid, Zhu, and colleagues of Tsinghua University in China have developed a strategy to isolate phenotypically-resistant mycobacteria. They will therefore be able to identify small molecules that are specific for this subpopulation as opposed to the bulk tuberculosis population, which may in turn identify pathways to accelerate TB therapy.

Ye Xiang of Tsinghua University in China will study enveloped virus glycoprotein structures as a means to better understand the mechanisms by which enveloped viruses infect their hosts. The results obtained will contribute to the general knowledge of enveloped virus infection and maturation in addition to providing important information for vaccine and viral drug design for enveloped viruses such as HIV.

Xinquan Wang of Tsinghua University in China will study the molecular mechanism of MERS-CoV neutralizing antibodies (MERS-4 and MERS-27) and further increase their potency by combining structural, biochemical, and virological methods.

Kaixia Mi of the Chinese Academy of Sciences in China will identify biomarkers that define the diagnosis and status of tuberculosis infection.

Yan Zhu of the University of Biophysics, Chinese Academy of Sciences, in China will build a system based on electroencephalography to monitor the activity of the fetal brain in utero. Due to technical and practical limitations, current methods for measuring brain activity are limited to newborns. However, analyzing development of the fetal brain would reveal new insight into very early stages of neurodevelopment, and could lead to improved treatments for certain disorders. They will adapt electroencephalography, which measures electrical activity in the brain, to detect the weaker signals of the fetal brain via multiple electrodes on the mother's abdomen, and build analysis software that can differentiate these signals from background noise. Once the prototype has been built, they will test it on humans to further refine the design.

James Zhijun Lu of Regenex Pharmaceuticals, Ltd. in China will reduce the thickness of natural latex condoms to enhance sensitivity during use. Current condom thickness is dictated by the relative strength of the material, which must be maintained to prevent disease transmission and unwanted pregnancies. However, thicker condoms inhibit sensation during use. Natural latex is weakened below a thickness of 40?m, mainly due to the formation of different sized aggregates in emulsion. To enable the production of thinner condoms, they will analyze whether optimizing the ratio of these aggregates can increase the strength of natural latex, and develop a new centrifugation process to remove aggregates during condom manufacture. They will also identify conditions, such as temperature, that may inhibit aggregate formation to further reduce thickness while retaining strength.

Jinlin Zhou of the Shanghai Veterinary Research Institute in China will develop anti-tick biological agents composed of double-stranded (ds) RNAs targeting two selected tick proteins to control the dominant tick species Rhiphicephalus haemaphysaloides, which causes human and animal diseases in south Asian countries. Previous control approaches using pesticides or vaccines have had limited success. Long dsRNAs, which silence target genes, have previously been used successfully to control a tick infestation in cattle. Zhou has selected two candidate proteins in R. haemaphysaloides, P0, which is required for viability, and Rhipilin-1, which is required for the tick to attach to the host. Zhou will synthesize dsRNAs against these proteins and test different liposome types and conditions for optimal delivery into the ticks, and evaluate the effect of the dsRNAs on tick survival and feeding.

Michael K. Chan of the Chinese University of Hong Kong in China and his collaborators will use dawadawa, a staple food in western Africa, as the basis of a novel therapeutic for treating and preventing multiple parasitic worm (helminthic) infections, which are prevelant in developing countries. Dawadawa can be produced by fermenting soyabeans with Bacillus bacteria. By engineering Bacillus to produce parasite-killing (antihelminth) proteins, they can make a staple food with therapeutic properties at low cost. The antihelminth proteins will be encapsulated within crystals that both protects them from degradation in the human gut as well as incorporating a chemical trigger for targeting release in the intestine, where most of the parasites reside.

Yonghong Wu of the Institute of Soil Science, Chinese Academy of Sciences in China will develop and test a periphyton biofilm fertilizer in paddy fields in Southern China, as a cheaper and easier alternative to chemical fertilizer. Periphyton is a mixture of microorganisms that grow on submerged objects in water. It is environmentally benign, can store large quantities of nutrients, and inhibit weed growth, making it attractive as a fertilizer. By selecting the optimal substrate and microorganisms for testing, the periphyton biofilm fertilizer could improve rice productivity and save labor.

Feng Qian of Tsinghua University in China will work to develop an inhaled drug particle using a scalable formulation process to deliver tuberculosis drugs directly into the lungs. They will develop micro-particles containing current TB drugs and will test their utility when inhaled.

Ruifu Yang of the Chinese Military Academy of Medical Sciences in China will develop a database of DNA fingerprints for various pathogens and microbes. This database will allow researchers to quickly identify the pathogen responsible for an emerging disease, as well as the origin of that pathogen.

Wanli Liu of Tsinghua University in China will use high-resolution, high-speed imaging to view and understand the interaction of B cells and viruses with the ultimate goal of developing a vaccine that generates broadly neutralizing antibodies.

Haiteng Deng of Tsinghua University in China will identify new candidate antigens for vaccines to prevent tuberculosis.

Yan Shi of Tsinghua University in China will use single-cell force spectroscopy to detect changes in red blood cells infected with the malaria parasite with the goal of developing methods to target antimalarial drugs specifically to infected cells.

Yuxing Chen of the University of Science and Technology of China will study a protein that is essential for survival for group B streptococcus, bacteria which can infect pregnant women and their newborns. They will characterize this protein and study its potential as both a drug target and vaccine antigen for developing new drugs and vaccines against group B strep.

Michael Chan of the Ohio State Research Foundation in the U.S. will develop an engineered strain of bacteria used to ferment beans in traditional Asian and African diets, to display an antigen from the Tuberculosis bacterium. The engineered bacillus will then be used to make the traditional Asian dish natto, which can serve as a kind of oral vaccine to elicit a strong immune response. If successful, this strategy can be used to introduce a variety of disease antigens through culturally accepted foods.

Gong Cheng of Tsinghua University in China will develop a transmission-blocking vaccine against dengue virus that takes advantage of blocking mosquito infection by targeting the transmission from human to mosquito.

Zhengsong Weng of Tsinghua University in China will use reverse vaccinology to seek new antigens for Streptococcus pneumonia to develop new vaccines against bacterial pneumonia.

Babak Javid of Tsinghua University School of Medicine in China will determine whether drugs that increase the accuracy of protein production in Mycobacterium tuberculosis, which causes TB, can boost the effect of existing TB drugs and thereby shorten the current 6 month treatment period. They hypothesized that resistance to TB drugs is caused in part by the ability of the bacterium to change its proteins by making random errors during their synthesis (known as mistranslation). In Phase I, they proved that this was indeed the case, and performed a screen to identify candidate drugs that improved the accuracy of protein production. In Phase II, they will perform a further screen and test whether the identified compounds can reduce therapy duration in two mouse models of TB infection.

Hua Wang of Tsinghua University in China will use reverse vaccinology, working backwards from host broadly neutralizing antibodies, to design and discover vaccines against HIV infection.

Yong Zhang of the National Institute for Viral Disease Control and Prevention in China will characterize vaccine-derived polioviruses (VDPV), which emerge from the widely used oral polio vaccine and can cause disease outbreaks, to aid surveillance and eradication efforts. Polio has been largely eradicated from many countries by vaccination. However, the vaccine itself is an attenuated form of the poliovirus that can revert back to a virulent form. In Phase I, they sequenced and compared the genomes of different types of VDPVs that have emerged in China to determine how the virus arises and circulates in the population. In Phase II, they will sequence more VDPVs and look for so-called mutation hotspots in the genome, which could lead to a safer and more effective vaccine.

Jing Ning of Beijing Sunnybreeze Technology Inc. in China will develop a human fecal waste disposal system that uses wind or solar power to load waste from septic tanks or cesspools into a column, where the waste dehydrates via solar energy, and then is combusted to kill remaining pathogens and reduce its volume. This system is designed to be affordable, durable, and low-maintenance, allowing for rapid, onsite waste disposal. In Phase I, while at Shijiazhuang University of Economics in China, Ning provided proof of principle that human raw sewage waste could be loaded into the facility and dried by solar evaporation. In Phase II, Ning, now with Beijing Sunnybreeze Technology Inc., will refine the design to better transport the heat generated by the solar collector using a thermal air blower, and develop a mini waste processor that uses a ball and screw mechanism to automatically transport, dry and sterilize the human waste. These components will be incorporated into a safe and affordable waterless toilet, which will be tested and further refined.

Quimin You of Ustar Biotechnologies (Hangzhou) Ltd. in China will develop affordable, rapid, and simple nucleic acid extraction devices and an affordable, rapid and simple isothermal nucleic acid amplification assay that can be performed at the village level by minimally trained personnel.

Hongxiang Chen of Union Hospital, Tongji Medical College, Huazhong University in China will develop X-ray-sensitive fluorescent nanoparticles conjugated to antibodies that will selectively bind to HIV. Once bound to the targets, the nanoparticles can be excited by X-rays to kill the virus.

Bin Fan of the Research Center for Eco-environmental Sciences in China seeks to develop a decentralized sanitation system which uses a low-cost waterless, vacuum system to collect excrement and kitchen waste. The combined waste can then be processed into organic fertilizer.

Guozhi Wang of the National Institute for Control Pharmaceutical & Biological Products in China will assess the effectiveness of a new inexpensive skin test that can differentiate between true Tuberculosis infection and the markers of the BCG vaccination. Because the current TB screening protocol is not sensitive enough to tell the difference, this new test could lead to earlier and better treatment options for those with early-stage infections.

Jintian Tang of Tsinghua University in China will design and test a portable, non-invasive device for its ability to kill the worm larvae that causes the chronic parasitic disease Schistosomiasis. Tang's research has shown that the worm larvae, which enters through the skin and causes immediate dermatitis, die at temperatures low enough to not harm human skin. By applying a heated device on the skin upon the first signs of dermatitis, the worm larvae can be eradicated before entering the human blood stream.

Chang Liu and Xiaohong Kong of Nankai University in China seek to develop a self-destructive virus vector called HIVi, which will express small interfering RNA to silence HIV in infected cells, and also replicate in a controlled manner to outcompete the HIV infection before turning itself off. The efficacy of HIVi in interfering with HIV will be assessed using a number of standard HIV cell-based assays.

Hongyue Dang, of China University of Petroleum (East China) will research whether early-stage pneumonia infection produces specific biomarkers that can be detected in a breath analysis. If so, Dang will produce and test a prototype breath sensor device that can be used in low-resource settings to capture and analyze these signature chemical compounds as a method to diagnose pneumonia.

Chen Yangchao of the Chinese University of Hong Kong proposes developing a lentiviral vector that targets the entry and replication of influenza viruses in domestic chickens. The team plans to test the ability of these modified chickens to be resistant to various influenza viruses in an effort to reduce the frequency of flu epidemics in poultry and, ultimately, in humans.

Guang-hong Tan of Hainan Provincial Key Laboratory of Tropical Medicine in China seeks to create a next-generation malaria vaccine by deleting a gene responsible for parasite development in the liver adding a new gene which attracts dendritic cells to the infection site. Using this modified sporozoite in a vaccine could produce a limited infection that, at the same time, induces a strong immune response against malaria.

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.

With evidence that microRNA can interfere with host immune response, Qian Gao of Fudan University in China will compare microRNA expression profiles of those with active and latent TB to detect which genes which have significant differences in expression.

Vaccines are urgently needed to slow the spread of HIV and hepatitis C virus (HCV), which together infect an estimated 240 million people, most of them in developing countries. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Deng and his colleagues are working to improve techniques for creating mouse models with immune systems and livers that are similar enough to humans to allow testing of potential HIV and HCV vaccines. The team is working to create chimerical mouse models with hematopoietic cells (HSCs) and hepatocytes differentiated from human embryonic stem (hES) cells.

Dr. Jiang's team is identifying components of human cells that microbes use to establish an infection and replicate but that are not essential to the human host. Better understanding of microbial replication and survival from the view of host cells, the project team anticipates, will provide a foundation for novel therapeutic approaches to combat infectious diseases while simultaneously providing a low likelihood of inducing drug resistance. These compounds could potentially work by interrupting microbes from creating the environment they need to replicate in human cells.