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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

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3-D Human Small Intestinal Organoid for Enteric Infections

Cirle WarrenUniversity of VirginiaCharlottesville, Virginia, United States
Grand Challenges Explorations
Enteric Disease Models
15 Apr 2014

Cirle Warren of the University of Virginia in the U.S. will develop a three dimensional cell culture model (organoid) of the human intestine to study diarrheal diseases. They will build the organoids in a bioreactor using three intestinal cell types, and test different scaffolds to simulate the complex cellular and structural architecture of the human gut. The organoids will then be infected with Cryptosporidium, a common cause of diarrhea in developing countries, and analyzed for altered structural and molecular characteristics to gain insight into the host infection response. This model could also be used to identify new drug targets and evaluate candidate drugs.

A Mouse Model for Heat-Stable Enterotoxin Diarrhea

James NataroUniversity of VirginiaCharlottesville, Virginia, United States
Grand Challenges Explorations
Enteric Disease Models
15 Apr 2014

James Nataro of the University of Virginia in the U.S. is developing new mouse models of environmental enteric dysfunction (EED) to explore how enteric pathogens commonly found among children in developing countries can affect intestinal function and cause growth retardation. In Phase I, they developed mouse models for five of the common pathogens and found that, as in humans, malnutrition (protein or zinc deficiency) enhanced the severity of infection, associated growth retardation, or the presence of intestinal inflammation. In Phase II, they will study the molecular mechanisms involved and analyze human candidate EED-associated biomarkers and metabolic states in their new mouse models to better compare them to the human disease. They will also test the effect of simultaneous and repeat infections on growth, and treat one of the models with alanine-glutamine to determine whether they can be used to evaluate new drugs.

A Pediatric Immune Enteroid Model of Gut Enteropathy

Marcela PasettiUniversity of Maryland, BaltimoreBaltimore, Maryland, United States
Grand Challenges Explorations
Enteric Disease Models
8 Oct 2014

Marcela Pasetti of the University of Maryland in the U.S. will generate an in vitro model of the gut using intestinal stem cells and immune cells to better mimic the damaged and inflamed guts of young children in developing countries for testing new treatments. Current so-called human enteroid models lack additional relevant cell types found in the intestine, particularly immune cells, which are known to play an important role in gut health and function. They will expose their new miniature pediatric gut model to enteric pathogens and test the ability of human breast milk and bovine hyperimmune colostrum to repair the subsequent damage.

A Small Animal Model of ETEC-Mediated Diarrhea

Sandhya VisweswariahIndian Institute of ScienceBangalore, , India
Grand Challenges Explorations
Enteric Disease Models
25 Apr 2014

Sandhya Visweswariah of the Indian Institute of Science in India will generate a mouse model for studying secretory diarrhea, which causes significant mortality in young children. Secretory diarrhea is often caused by the bacterium Escherichia coli, which produces a toxin that binds to a cell surface receptor (the guanylyl cyclase C receptor) in the gastrointestinal tract thereby causing diarrhea. They will genetically engineer a mouse in which they can hyperactivate this receptor specifically in intestinal cells to potentially trigger secretory diarrhea. The effect on the gastrointestinal tract and any accompanying molecular changes will then be analyzed and could lead to the discovery of new therapeutic targets.

Abate: Human-Scented "Trojan Cows" Kill Vectors of Disease

Agenor Mafra-NetoISCA Technologies, Inc.Riverside, California, United States
Grand Challenges Explorations
Human and Animal Health
17 Apr 2014

Agenor Mafra-Neto of ISCA Technologies, Inc. in the U.S. will test whether an artificial lactic acid treatment (called abate) can trick disease-transmitting insects such as mosquitoes into infecting animals rather than their preferred human hosts, thereby reducing infection rates. Malaria-causing parasites are carried by mosquitoes, which identify the human hosts that help them reproduce by detecting the high levels of lactic acid in human perspiration. Cattle are resistant to malaria and many other human diseases transmitted by insects, and are often treated with deworming medication, which has a toxic effect on mosquitoes and their parasites. They will develop a stable formula of abate and test its effect on altering host choice of several disease-transmitting insects to determine which is most effective.

Adolescents and Youth Taking Control of their HIV Treatment

Peter GichangiInternational Centre for Reproductive Health KenyaMombasa, Kenya
Grand Challenges Explorations
Behavior Change
9 Apr 2014

Peter Gichangi of the International Centre for Reproductive Health Kenya in Kenya will develop a website for 10 – 24 year olds with HIV to help guide them safely through adolescence and improve adherence to treatment. This age group experiences unique physical and emotional stresses, and for those with HIV, adherence to treatment is relatively low. They will develop and launch a secured website in consultation with the target age group to enable individuals to access HIV-related information; query health professionals, including the possibility for live chats; participate in forums; and retrieve their personal treatment data. They will set up a randomized study and evaluate their approach by measuring number of users and web behavior, and whether it increased adherence to treatment and appointment visits.

Agriculture Innovation Changing Health and Nutrition Behaviors

Mary-Lynne LascoINMED Partnerships for ChildrenAshburn, Virginia, United States
Grand Challenges Explorations
Community-Based Interventions
3 Oct 2014

Mary-Lynne Lasco of INMED Partnerships for Children in the U.S. will evaluate whether on-site sustainable food production and associated education in schools improves child health when combined with semi-annual deworming treatments and a new school feeding program in Peru. Many Peruvian children are malnourished, and soil-transmitted helminth infections are endemic and a significant cause of mortality. They will study two primary schools in Peru's Ucayali region, one of which will receive an aquaponic system, comprising fish farming and growing plants without soil, to produce healthy food and to educate children, teachers and parents on the value of eating healthily. They will analyze the effect of aquaponics and integrated education on nutrition and helminth infection rates at the schools, as well as on the attitudes of parents and the community.

Air-Infused Female Condom

Mache SeibelHealthRock LLCNewton, Massachusetts, United States
Grand Challenges Explorations
Next Generation Condom
10 Apr 2014

Mache Seibel and team from HealthRock, LLC in the U.S. have invented a female condom that is inflated and positioned using air pressure and provides additional stimulation, which they will test in the laboratory and in clinical trials. The only available female condom has not been widely accepted partly because it is difficult to position, conspicuous, reduces sensation, and can make sounds during use. The new condom is made from polyurethane to minimize sound emission, and the inflation mechanism ensures quicker insertion. The shape is also designed to enhance sensation for both the male and female during intercourse.

An EEG System to Measure Fetal Brain Development

Yan ZhuInstitute of Biophysics, Chinese Academy of SciencesBeijing, China
Grand Challenges Explorations
Brain Function/Gestational Age
9 Oct 2014

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.

An Integrated Human Enteroid Model of EED

Honorine WardTufts Medical CenterBoston, Massachusetts, United States
Grand Challenges Explorations
Enteric Disease Models
10 Apr 2014

Honorine Ward of Tufts Medical Center with Mary Estes at Baylor College of Medicine in the U.S. and Gagandeep Kang at Christian Medical College in India will develop a three dimensional cell culture model (enteroid) of the human intestine to study environmental enteric dysfunction (EED), which is associated with substantial morbidity in young children in the developing world. They will grow enteroids from isolated intestinal crypts derived from unused surgical samples from children with and without EED in India. They will study the structure and function of these enteroids and their value as a model of EED by analyzing biomarkers in associated blood and stool samples. Once validated, they will supplement the model with immune cells and gut microbes that they will co-isolate from the same individuals to develop a 'mini-gut' model that more closely mimics the human disease, which can be used to develop and evaluate targeted therapies.

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