Growth factor free strategy for therapeutic neo-vascularization

Student of Indian Institute of Technology, Madras Shivam Chandel and Abel Arul Nathan S won the award for a Growth factor free strategy for therapeutic neo-vascularization. They carried her project work under the guidance of Dr. Madhulika Dixit.

Endothelial progenitor cells (EPCs), a subset of circulating mononuclear cells are currently being studied as candidate cell sources for revascularization strategies. Increasing the number and/or improving the function of EPCs may be promising in the treatment of atherosclerotic disease, ischemia or Heart Failure. Current therapies for neo-vascularization are based on the administration of growth factors and nitric oxide donors. Administration of NO-donors has been promising but failed to promote neo-vascularization particularly in elderly and diabetic patients. Several clinical studies using growth factors have failed in phase II which successfully passed phase I, either due to their short half-lives or due to their harmful side effects. Studies have shown that application of fluid shear stress induces the differentiation of mononuclear cells to endothelial cells. Shear stress also enhances capillary blood flow and modulates the function and expression profile of angiogenic genes. However, the effect of shear stress on the circulating mononuclear cells is not well characterized. Hence, to study the effect of shear stress on the angiogenic potential of circulating mononuclear cells, a cone plate-based instrument assembly has been developed. This study focuses to enhance the angiogenic potential of mononuclear cells through ex-vivo preconditioning via application of shear stress.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Shivam Chandel and Abel Arul Nathan S, Indian Institute of Technology, Madras at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

 

Low-cost, easy-to-use, in-house developed electric cell impedance sensing (ECIS) system for studying the dynamic behaviour of the biological cell

Student of Indian Institute of Technology (Banaras Hindu University), Varanasi, Uvanesh Kasiviswanathan won the award for research work of Low-cost, easy-to-use, in-house developed electric cell impedance sensing (ECIS) system for studying the dynamic behaviour of the biological cell. He carried their project work under the guidance of Prof. Neeraj Sharma, Dr Sanjeev Kumar Mahto.

Physiological properties of each and every living organism (either diseased or normal) changes randomly with the external environmental conditions. Thus, the continuous monitoring of these properties is crucial for both long and short term analysis of any particular in vivo models. Generally, a large number of animals are used as in vivo models to analyse and predict the effect of various synthesized/formulated moieties and moreover they are being sacrificed as and when required during the drug screening process. In addition, in the pre-clinical and clinical trials/stages such step leads to a huge failure rate not only due to differences in the in vitro and in vivo models selected but also because of the incompatibility issues concerning to the sensing devices utilized for both the models.

Thus, an improved measuring/screening platform that can interface with both the in vitro and in vivo models need to be developed for measuring the dynamic behaviour of any biological cell/system. This study has designed and fabricated a low-cost, easy-to-use, portable electric cell impedance sensing (ECIS) system that shows great potential for analysing the physiological parameters in real-time both for in vitro and in vivo models. It is important to note that our device, by any means neither affects nor influences the biological models being tested. Further, the experimental data can be correlated with the physiological parameters through a theoretical calculation of the lumped-elemental electrical parameters of cell-electrolyte interface and metal-electrolyte interface.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Uvanesh Kasiviswanathan, Indian Institute of Technology (Banaras Hindu University), Varanasi at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

Revelation of G-quadruplex formation as a molecular basis of fragile X tremor/ataxia syndrome (FXTAS) leads to a new direction in the drug discovery

Students of Indian Institute of Technology, Hyderabad Yogeeshwar Ajjugal and Narendar Kolimi won the award for research work of Revelation of G-quadruplex formation as a molecular basis of fragile X tremor/ataxia syndrome (FXTAS) leads to a new direction in the drug discovery. They carried their project work under the guidance of Dr Thenmalarchelvi Rathinavelan.

Trinucleotide repeats belong to the family of microsatellites (a tract of 1 to 6 repetitive nucleotides) that are commonly observed in eukaryotes and exhibit repeat length polymorphism. The inherent ability of trinucleotide repeats is to undergo abnormal expansion (viz. increase in repeat length) which leads to many incurable genetic disorders that are mainly neurodegenerative.

For instance, CGG repeat overexpansion in the 5’ untranslated region (UTR) of fragile mental retardation (fmr1) gene from unusual nucleic acid conformations and it causes genetic instabilities. This results in fragile X syndrome (FXS) and fragile X tremor/ataxia syndrome (FXTAS). We have shown here that the number of G…G/C…C mismatches dictate the secondary structural choice of the sense and antisense strands of fmr1 gene and the corresponding transcripts. Circular dichroism (CD) spectra reveal that CGG sense strand and its transcript favour quadruplex structure due to the intolerance for periodic G…G mismatch in a hairpin/duplex. Further, CD and molecular dynamics simulations show that more than four C…C mismatches cannot be accommodated in an RNA duplex consisting of CCG repeat (antisense transcript), instead, i-motif structure is favored. In contrast, CCG can form hairpin/duplex structure at the DNA (antisense strand) level irrespective of the number of C…C mismatches. Such unusual structures may be responsible for the increased R-loop stability, bidirectional transcription, RNA foci formation and repeat associated non-AUG translation for monopolypeptide aggregates in FXTAS, a mechanism similar to C9ORF72 GGGGCC repeat expansion that causes amyotrophic lateral sclerosis. The results presented here also suggest that G-quadruplex structure observed in fmr1 gene and its transcript can be a potential drug target.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Yogeeshwar Ajjugal and Narendar Kolimi Indian Institute of Technology, Hyderabad at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

Modernization of traditional anti-malarial drug artesunate via nanomedicine approach

Students of Shiv Nadar University, Uttar Pradesh, Deepika Kannan, Nisha Yadav,  won the award for research work of Modernization of traditional anti-malarial drug artesunate via nanomedicine approach. They carried their project work under the guidance of Dr. Shailja Singh, Dr. Bimlesh Lochab, Dr. Soumya Pati.

The burden of malaria has been prevailing since ages in India with a death toll of 1.31 million per year. The failure in combating the disease has been attributed to the drug resistance, limited efficacy of the drug or lack of immunogenicity of vaccine antigens against all strains of plasmodium. In our study, we have applied a smart strategy to deliver the drug along with its catalyst (ferrous ion) in a sustainable manner which will help in improving the therapeutic effect of the drug. The novel innovative approach undertaken in the study has showcased the efficiency of surface coated iron nanoparticles as enhancer of the anti-parasitic activity of artesunate in vitro. This further succour the targeted delivery of the drug and the nanoparticle to the parasite’s food vacuole. The site of action being acidic in pH, the particle mediates delivery of the drug and ion in a slow-release manner. Slow dispersion enables a constant mode of action of the drug rather than an outburst. Thus, a continuous source of radical species is released. Since in combination with nanoparticle the drug remains in the active state for a prolong period, the damages occurring to the parasite is extensive as compared to the drug without nanoparticle. Further observation interpreted that in vitro the measure of ROS within drug+nanoparticles treated parasites were elevated as compared to the drug-treated parasites. Additionally, increased ROS exerted increased DNA and protein damage (in terms of carbonylation and alkylation).

Though the mechanism of free iron uptake by the plasmodium is still inconclusive, difficulty in protecting the human population against malaria by using iron nanoparticle is highly debatable. Based on the in vitro studies observation for the first time was deciphered that the surface coated iron nanoparticle alone did not affect the parasite growth. However, the results demonstrated iron nanoparticle together with artesunate depicted reduced parasite load in a dose dependent manner. In vitro and in vivo data indicated the combination exhibited ~5 folds (IC50 value of 0.4nM) decrease in the dosage level as compared to artesunate alone (IC50 value of 2nM). The fabrication of the nanomedicine provides a means to eliminate the parasite load sustainably such that the effect of the drug is prolonged, providing a mode of complete parasite clearance.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Deepika Kannan, Nisha Yadav, Shiv Nadar University, Uttar Pradesh at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

Magnetic-field actuated hybrid nanofiber scaffold and apparatus for 4D tissue engineering

Students of Indian Institute of Technology, Roorkee Uday Kumar Sukumar and Vinay Kumar won the award for research work of Magnetic-field actuated hybrid nanofiber scaffold and apparatus for 4D tissue engineering. They carried their project work under the guidance of Dr P. Gopinath.

The present invention provides a hybrid multi-layered nanofibrous scaffold and a four-dimensional dynamic cell culture apparatus. The pre-existing 3D scaffolds in the market does not address the dynamic culture conditions covered in this technology, therefore, they do not represent the in-vivo conditions as closely as the 4D scaffold proposed in this research work. The market of 4D scaffolds is focussed on the area of therapeutics and diagnostics. 4D scaffolds are expected to reduce the need for animal disease models, as they are versatile in accustoming to different culture conditions, and are more relevant for cell culture studies as compared to 3D scaffolds. Furthermore, the scaffold is biocompatible and operates in non-contact mode and it is precisely controlled across all 3- dimensions. The hybrid scaffold apart from providing the extracellular matrix (ECM)-like scaffold, also meticulously simulates the mechanical stress cycles that cells experience under the in-vivo conditions.

For monitoring cells on a real-time basis under microscopes, the apparatus is provided with sufficient headspace over the tissue culture plate for positioning a microscope lens. The circular slot provided at the base of the apparatus perfectly accommodates cell culture plates and also enables easy transmission of light during microscopic observation without any interference of the apparatus body. Cell plasticity, differentiation and cancer metastasis are determined to a large extent by cell adhesion and surface proteins which are effectively recapitulated in this scaffold. The scaffold serves as a realistic and relevant platform for studying the role of cytoskeletal proteins and focal adhesion proteins in various diseases in the fields of cardiology, dermatology, metabolism, gastroenterology, oncology and orthopaedics.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Uday Kumar Sukumar and Vinay Kumar, Indian Institute of Technology, Roorkee at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

Yog-I – An affordable insulin pump for Type-1 diabetic patients in resource constrained settings

Students of Indian Institute of Science, Bangalore, Deval Karia, Rohit S. Nambiar won the award for research work of Yog-I – An affordable insulin pump for Type-1 diabetic patients in resource-constrained settings. They carried their project work under the guidance of Dr Manish Arora.

Numerous studies have been extensively documented for the benefits of Continuous Subcutaneous Insulin Infusion (CSII) over Multiple Daily Injections (MDI) for insulin therapy in Type 1 Diabetes Mellitus (T1DM) patients. Despite such overwhelming evidence in support, adoption of CSII is sparse, particularly in resource-constrained settings like India. Apart from the institutional factors, fixed and recurring costs of such a device are often found to be a withholding factor for widespread application. The abstract describes the development of a novel, affordable insulin pump for T1DM patients matching the specifications of a state-of-the-art pump, while significantly bringing down the fabrication cost. Most pumps rely on a lead screw/nut coupled with a geared DC motor to achieve precise micro-motion.

 

 

 

 

 

 

These motors typically make use of micro-gears as a means of speed reduction, which is inherently expensive to manufacture. Consequently, they contribute significantly to the final cost of a pump. In this work, we take an innovative approach to distribute the requisite speed reduction in multiple stages, with an acceptable compromise on the product size. The system is actuated by a nominal DC geared motor and a novel mechanism of converting continuous rotary input to intermittent output. The kinematic chain is feedback-controlled which ensures volumetric accuracy of the delivered fluid. The pump can be wirelessly controlled via a remote. The same wireless channel can be used to connect to a Continuous Glucose Monitoring (CGM) device for subsequent integration with an Artificial Pancreas system. Preliminary accuracy tests showed promising results when compared with commercially available devices.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Deval karia,Rohit S. Nambiar, Indian Institute of Science, Bangalore at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

 

Anti-Pesticide Dermal Gel

Students of Instem, Bangalore, Ketan Thorat and Subhashini Pandey won the award for research work of Anti-Pesticide Dermal Gel. They carried their project work under the guidance of Dr Praveen Kumar Vemula.

Due to lack of resources, spraying pesticide using the hand-held manual device is a norm in Indian agriculture. In the past three years, more than 3000 farmers in India were hospitalized due to an alarming frequency of pesticide exposure which eventually led to a tragic toll of 442 deaths. This severe clinical gap has a massive impact on the health of 263 million farmers and their families in India. Considering the above facts, the study has been conducted to develop a skin-gel that can protect the farmers from the harmful effects of pesticides. The skin-gel constituted with numerous chemical detoxifiers when applied, instantly attacks the pesticide molecule and catalytically cleaves it into smaller, non-harmful components, thereby diminishing the toxic effect of pesticide.

Usually, the skin is exposed to a large amount of pesticide which transdermally enters the body. Over time, these farmers are further exposed to multiple small doses of pesticides during spraying and handling at farms which leads to an accumulated, irreversible health damage resulting to learning difficulties, suffocation, paralysis, muscle weakness, loss of stamina, and in certain cases-death. This impact affects healthcare costs and major socio-economic implications. The distinctive feature of this study is to formulate a skin gel that safeguards the transdermal route undertaken by the detrimental pesticide molecules to enter the human body. The pioneering work of this skin-gel technology lies in the fact that each detoxifier can detoxify multiple pesticide molecules. Therefore on a single application, it offers a 24 hr protection against pesticides

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Ketan Thorat and Subhashini Pandey, Instem, Bangalore at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

Development of engineered E.coli for high-throughput drug screening against Malaria and Kala-azar

Student of Jawaharlal Nehru University, Delhi, Preeti Yadav won the award for a Development of engineered E.coli for high-throughput drug screening against Malaria and Kala-azar. She carried her project work under the guidance of Dr. Shailja Singh, Dr. Swati Garg, Dr. Soumya Pati.

Eukaryotic parasites increase the functional diversity of their proteome through a number of post-translational modifications (PTMs), to facilitate their survival and replication. Palmitoylation is one of the important PTM present in eukaryotic cells that modulate protein-protein interactions and plays a major role in several diseases like Cancer, Diabetes, Schizophrenia, Alzheimer’s, Malaria, Leishmaniasis, etc. In malaria parasite, Plasmodium falciparum, 10% proteome have been found to be palmitoylated that plays a crucial role in disease progression and pathogenesis, while in Leishmania donovani, we have reported that 25% of the total proteome gets palmitoylated and is involved in flagellar motility, vesicular trafficking and invasion. Plasmodium falciparum and Leishmania donovani encodes for 12 and 20 Palmitoyl acyl transferases (PATs) respectively that transfer palmitate group to target protein. Being a major contributor of parasite-diversity, palmitoylation has not been explored as a chemotherapeutic target yet due to paucity of high-throughput assays.

Prevalence of drug resistance demands immediate action to search for newer drugs and newer targets. We have developed a novel strategy involving engineered E. coli to study parasite-specific palmitoylation. E.coli is a palmitoylation machinery-null system, but our in-silico study suggested that 110 proteins of E.coli contain sites for palmitoylation. Thus, these E.coli proteins can serve as substrates for parasite-specific PATs expressed in E.coli. Parasite PATs were cloned and expressed in E.coli in the presence of PAT inhibitor and palmitoylation status of E.coli was analysed using Click chemistry. The inhibitor, 2-Bromo-palmitate that we have used here acted both as anti-malarial and anti-leishmanial as deduced by parasite growth-inhibition assay and invasion assay respectively. This is the first ex-vivo study of parasite-specific modifications in E.coli, that could be used as a robust, high-throughput screening tool for anti-protozoan drugs targeting palmitoylation, thus helping in the development of novel anti-parasitic molecules.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Preeti Yadav, Jawaharlal Nehru University, Delhi at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

 

Novel hybrid Technology for Bioseparation

Student of Institute of Chemical Technology, Mumbai Jayeshkumar Sevantilal Mevada won the award for research work of Novel hybrid Technology for Bioseparation. They carried their project work under the guidance of  Prof. Aniruddha B. Pandit.

In Current era, the unaffordability of medicine to rural peoples and pollution of the river are the big issues for the developing countries. A biological approach is an alternative way for the replacement of hazardous chemical processes responsible for water pollution, but the cost is the primary concern for its applicability. The microbial cell is the factory of various biological products located intracellularly or extracellularly. 

Conventional method (High-pressure homogenizer) causes the complete cell disruption which results in the release of all the contaminating materials with the target product of interest. This contaminating materials restrict further purification which leads to problems such as membrane fouling, higher processing times, reduced life of chromatographic column, increase in the steps of purification (10-13 steps) and higher cost of purification (70 to 80 % cost of total production cost).

We have developed novel hybrid technology where controlled cavitation using the hydrodynamic cavitating device was used for the selective recovery of intracellular biomolecules at microbial cell disruption stage (with a pretreatment regimen of acidic as well as alkaline conditions). Synchronizing of pretreatment and cavitating conditions result in selective recovery of biomoleculesfrom the cytoplasmic and periplasmic location of cells with minimal contaminating materials. The developed technology is believed to be novel and a breakthrough in the field of bioseparation. The expensive multi-bioseparation steps can be avoided because of the selective recovery of biomolecules at the initial stage. The uniqueness of this invention when compared with the existing technologies augment its characteristics in selectiveness, energy efficiency, easily scalable, reduced number of steps (from 10-13 to 3-5), low overall cost (3-4 times), 4-5-time reusability of immobilized product. Apart from the aforementioned qualities, the cost reduction by the developed technology can be considered as the big initiative step toward the greener processes and affordable cost biotherapeutics.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Jayeshkumar Sevantilal Mevada, Institute of Chemical Technology, Mumbai at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.