A PMU-BIRAC INITIATIVE IN PARTNERSHIP WITH
THE BILL AND MELINDA GATES FOUNDATION
& IKP KNOWLEDGE PARK
TO IDENTIFY, NURTURE AND EMPOWER REVOLUTIONARY IDEAS
THAT ADDRESS GLOBAL HEALTH CHALLENGES
2017-Round 2 (Grand Challenges Explorations – India)
1. Dr. Pratap Mukhopadhyaya from Wobble Base Bioresearch Pvt. Ltd. has proposed to develop a glucometer to detect HIV (Viral) RNA. The existing three major methodologies for viral load quantitation are the reverse transcriptase-polymerase chain reaction, the nucleic acid sequence-based amplification and branched chain DNA (bDNA) technique, require sophisticated infrastructure and reagents that generate high priced tests (>50 USD per test) which are often not feasible for use in resource limited settings.The assay involves amplification of viral RNA and its detection by the use of glucometer. RNA from lysed viral particles in serum is trapped using specially designed device containing padded silica-coated filter paper, ethanol washed and eluted for reverse transcription which is subsequently amplified using the LAMP based method. The amplified cDNA is then captured onto streptavidin-coated magnetic beads coated with specific capture-probe and concentrate HIV targets. This is then hybridized to complementary DNA-invertase enzyme conjugate to make HIV cDNA-DNA-invertase complex. This complex is added to sucrose solution to generate glucose through hydrolysis by invertase enzyme that is detected using glucose meter. The amount of glucose detected is a function of HIV copy number.
2. Mr. Balaji Teegala from BRUN Health Pvt. Ltd. has proposed to develop a Doppler stethoscope-Acousta which acts both as a standard annular Y-shaped stethoscope and as a Doppler stethoscope. The problem in auscultating the fetal heart to identify birth asphyxia among other fetal morbidities is the difficulty, skill, and training needed while using a regular stethoscope. This is mitigated by active sensing systems like the fetal Doppler systems or cardiotocographs. However, these systems are a burden to carry in
addition to a stethoscope. Alternatively, Electronic stethoscopes indicate clarity during auscultation but are predominantly targeted at specialties like cardiology while
still passive in their approach to sensing physiology.
Acousta is a combinatorial yet different approach using both the above systems. The
current functional prototype comprises of sensors implanted in a regular stethoscope
head integrated with a complete custom-electronics solution to evaluate
performance. The custom-electronics solution comprises a power management
module, a demodulation module and signal conditioning system to provide a clean
filtered output of the signal. In addition, preliminary work has been done to model
vibrational acoustics and its responses to the stethoscope construction proposed.
3. Dr. Taslimarif Saiyed from Centre for Cellular and Molecular Platforms (C-CAMP) will work to develop Microfluidics-based pH sensors for AMR detection. Anti-microbial Resistance (AMR) is big healthcare challenge worldwide, more so in India. Through susceptibility assay, it is vital to study emergence of new AMR strain(s) in a community or geography especially during epidemics. The device called Rapid Personalized Antibiotic Susceptibility Assay (r-PASA) is a DNA based assay with pH sensors on a microfluidics platform. Microfluidic channels have been chosen due to its suitability for rapid bacterial growth. Reaction mechanism involves the accumulation of organic acids as a function of bacterial growth which changes pH of growth medium. Since testing pH at microliter (<5 μl) or nano-liter volumes is challenging the device includes a DNA sensor which has a C-rich segment that bears a donor fluorophore and a mismatched duplex positions an acceptor fluorophore far apart. At acidic pH, the mismatched duplex frays as the C-rich strand forms an i-motif, bringing the two flourophores close together for a Fluorescence Resonance Energy Transfer (FRET) reaction that can be monitored by fluorescence imaging. The microfluidic channels also use various classes of commonly used antibiotics in at different concentrations to be able to ascertain resistance and quantify at the same time. They have also designed a reader that can monitor the FRET reaction which will be integrated into the device.
4. Dr. Gautam V Soni from Raman Research Institute will use Resistive Pulse Technique (RPT) for Malaria detection based on the established fact that the Plasmodium Falciparum infected RBCs are about 3 to 10 times stiffer than the normal RBC depending on the stage of parasite growth. Therefore, flow velocities of stiffer (infected RBC) and softer (normal RBC) cells can be easily distinguished in a simple fluidic channel using RPT. In this proposal, the difference in these flow velocities would be electrically measured across a spatial constriction to accurately determine the infected stage of individual RBCs.In 18 months, various aspects of the device would be optimized such as the probe tip, working pressure, POC electronics and software for high throughput detection.At the end of 18 months, they propose to build a portable electrical device capable of high sensitivity detection of 1 infected RBC per microliter of blood and also identify a clinical partner to work with infected blood samples from patients.
5. Arogya Medtech Pvt. Ltd. owned by Dr. Abhijit Das will work on developing a device- CEREBROS, which is a modular unit that combines electroencephalography (EEG) and near infrared spectroscopy (NIRS) to identify signatures and an IoT component integrated with a telemonitoring platform. This allows continuous remote monitoring of cerebral hypoxia and seizures and early detection and management of HIE at point-of-care. The device is in the form of a wearable cap over the head of the neonates. The device will also consist of a multivariate classifier incorporating quantitative EEG metrics and cerebral oximetry metrics, which will identify disease specific patterns that can be presented remotely by a neonatologist simultaneously in voice, text, pictures or video or animations.The device has been proposed to be provided to care providers, both Public and Private, under an affordable Rental or Pay-per-use model.The device provides an easy to use alternative to structural imaging using CT or MRI that has better sensitivity and specificity especially for neonates or infants less than 2 years old.
2017-Round 1 (Grand Challenges Explorations – India)
1. Dr. Asif Mohmmed from International Centre for Genetic Engineering and Biotechnology will work on identifying miRNA patterns and their correlation with the TB treatments response, treatment outcome and possible resistance generation. The selected miRNA pattern will be a valuable evaluation biomarker to predict response to anti-TB therapy, distinguish fast and slow responders to treatment and thereby offer early information to predict possible drug resistance development or individualised shorter drug regimens. Circulating miRNAs patterns are promising molecular markers for diverse pathological conditions and may aid in diagnosis, prognosis and monitoring treatment response. Patients will be followed up during their course of treatment with first line anti-TB drugs, and the team will isolate, sequence, identify and quantitate circulating miRNAs in sputum and plasma of these individuals at one month, two month and 6/9 months of treatment. miRNA patterns will be identified as potential biomarker as per Receiver Operating Characteristics, to identify quantitative patterns of circulating human miRNAs which can be used as early biomarker to predict outcome of the anti-TB drug therapy.
2. Dr. Sudeshna Adak from OmiX Research and Diagnostics Laboratories Pvt Ltd. will work on developing a point of care AMR test and polymer card combined with a phone based surveillance system to detect and track AMR molecular signatures in primary care settings or settings where access to AMR testing is currently unavailable. She will also demonstrate proof-of-concept for detection of AMR in urinary tract infections (UTI), establish and validate a 5-gene AMR signature assay in the proposed AMR test. Target genes are CTX-M-15 for Cephalosporin resistance, NDM-1 for Carbapenem resistance and Fosfomycin resistance, genes fosA, fosA3, fosB for antibiotic stewardship of Fosfomycin. The test will be demonstrated on the proprietary polymer card with the results comparable to an in-lab assay. The smart-phone application for AMR surveillance will be deployed on at least 3 smart-phones and tested in 10 locations. The entire system will be deployed at one primary health center.
Note: GCE-India was earlier piloted as the IKP Grand Challenges Explorations Program. Over the last 3 rounds, the winners were: Link to winners is here
November 2011 – Call 1 (IKP Grand Challenges Explorations)
1. Dr. Kanury Rao, from the International Center for Genetic Engineering and Biology (ICGEB), New Delhi. Dr. Rao proposed an alternative chemotherapy strategy to target TB, by modifying host proteins to inhibit the activity of the bacteria. Dr. Rao and his partner Sphaera Pharma are working on developing molecules that inhibit 3 host factors, that will reduce the infection of MDR/XDR strains, and can be combined with other drug regimens as a cure for TB.
2. Dr. Ganesan from Institute of Microbial Technology (IMTech), Chandigarh. K. Ganesan and Pradip Sen of the Council of Scientific & Industrial Research – Institute of Microbial Technology in India will work to selectively kill cells latently infected with HIV by engineering reagents that would initiate killing only upon specific binding to proviral DNA. If successful, further development could result in a possible cure for latent HIV, which is thought to block the ability of anti-retroviral drugs to fully eradicate the disease.
November 2012 – Call 2 (IKP Grand Challenges Explorations)
1. Dr. Ashish Ganguly, CSIR-Institute of Microbial Technology, Chandigarh and colleagues from the CSIR-Institute of Microbial Technology will make an affordable paper-based diagnostic to quickly and precisely measure plasma gelsolin levels in expectant mothers to help predict premature delivery and postpartum recovery, thereby reducing new mother and child mortality rates. They will determine the value of plasma gelsolin levels for predicting postpartum-related problems using patient sampling and an animal model of preterm birth. They will also develop the diagnostic by identifying a plasma gelsolin binding peptide that will be used to coat an optimized paper strip, along with a cell phone based read-out to enable remote analysis by a centralized unit.
2. Windmill Health Technologies, New Delhi comprising Dr. Avijit Bansal and Dr. Ayesha Chaudhary will develop an easy-to-use device to enable front-line health workers to more successfully resuscitate newborns. The current bag and mask device is inefficient and requires two trained personnel who are often not available. They have designed a foot operated manual resuscitator that also reports real-time performance, and requires only one trained operator. They will measure performance parameters of the prototype to generate evidence to support progress into clinical trials.
3. Dr. Rohit Srivastava and Dr. Aravind Kumar from the Indian Institute of Technology, Bombay in India will develop a microneedle-based drug delivery system for the treatment of tuberculosis (TB). Current treatment involves frequent administration of combinations of toxic drugs, which often leads to non-compliance necessitating further complex treatments. They have designed a photo-thermosensitive nanocarrier based on liposomes that can release the drugs transdermally via microneedles upon exposure to sunlight or LED in a controlled manner, bypassing the need for multiple administrations and reducing toxic side effects. They will fabricate the microneedles, evaluate drug release dynamics using light, and test drug bioavailability in vivo using a small animal model.
4. Dr. Vishwas Joshi, Founder of Seagull BioSolutions and team in India will develop a vaccine against the dengue virus by engineering a defective version of the measles virus to express dengue virus proteins (a so-called virosome), which can induce protective immunity. There is currently no approved vaccine that protects against dengue infection, which causes disease in 50-100 million people annually, some of which are life threatening. They will test the efficacy of the virosomes to prevent dengue virus infection by using them to vaccinate mice and analyzing immunity upon viral exposure.
November 2013 – Call 3 (IKP Grand Challenges Explorations)
1. Dr. Debjani Paul from IIT Bombay, is developing an Accurate, Accelerated and Affordable Kit to Predict Sickle Cell Disease Using Microfluidics and Cell Phone-based Imaging Systems. Current diagnostics require expensive equipment and trained personnel, and are often inaccessible to the rural populations most in need. They will produce a microfluidic chip that can preserve a sample of blood in the deoxygenated environment required to maintain its characteristic sickle-shape, which can then be detected by a modified mobile phone camera and automated software that they will also develop. The system will be tested for sensitivity and specificity using blood from patients with sickle cell disease.
2. Dr. Sanjiban Banerjee, founder of AbGenics Life Sciences is working on treatin intestinal worm (helminth) infections using modified probiotic strains of the bacterium Lactobacillus. Lactobacillus, which can live in the human gut, will be modified to produce stable RNA molecules selected to target specific helminth genes and ultimately destroy the parasite, thereby curing the infection. Because Lactobacillus colonizes the gut, it can be used as a long-term treatment for multiple helminth infections. Efficacy of the approach will be tested in hamster and rabbit models of intestinal worm infections.
3. Kouichi Hasegawa of the Institute for Stem Cell Biology and Regenerative Medicine in India will develop an assay using human liver cells to study the parasite Plasmodium vivax, which causes malaria, and to screen for new anti-malarial drugs. During the parasitic life cycle inside human hosts, P. vivax infects hepatocytes (liver cells), where it can lie dormant and protected from treatment, leading to disease relapse. To identify new drugs to target this stage of P. vivax requires large numbers of human liver cells, which are difficult to obtain and often unsuitable. A new approach will be used to generate human hepatocytes by isolating a type of white blood cell from individuals infected with P. vivax, and inducing them to differentiate into hepatocytes, which should better support parasite growth. Once validated, this P. vivax liver-stage culture system will be used in a preliminary screen of a set of chemical compounds to identify new anti-malarial drugs.