Top Research By Indian Bioscientists In 2019
The year 2019 observed groundbreaking discoveries from human cell regeneration for growing organs, to banishing genetic disease through breakthrough gene-editing techniques. It also witnessed some amazing discoveries across various fields of science. Scientists have made breakthrough discoveries this year.
This year Scientific research has made our lives safer & easier. And the life science community is only getting started.
Researchers in India have worked tirelessly to change our lives, so it’s worthwhile to take a step back and applaud their tremendous efforts. As you read this, the world of tomorrow is being shaped, so let’s have a look at Top Research By Indian Bioscientists In 2019
1. Peptidoglycan as a potential target for antibiotic action – CCMB, Hyderabad
Probably one of the most interesting works in this year is the extensive research conducted by Dr. Manjula Reddy, Chief Scientist at the Center for Cellular and Molecular Biology(CCMB), Hyderabad, on the biological processes involved in the synthesis and degradation of bacterial cell walls. Dr. Reddy’s work includes the identification, isolation, and characterization of ‘spacemaker’ enzymes which break down the cell walls to make space for new growth and most importantly can help in identifying potential targets for antibiotic action. She has even been awarded the Infosys Prize 2019 in the category of Life Science for her astonishing discovery.
Bacteria have an extra layer of protection called the peptidoglycan (PG) layer. It is a cross-linked mesh-like macromolecule consisting of glycan strands interlinked by short peptides. The cytoplasmic membrane is completely encased by the peptidoglycan. Therefore, for the cell to grow, cleaving these peptide cross-links is a prerequisite to making space for the incorporation of nascent glycan. In most of the bacteria, these peptides consist of d -glutamate, d -alanine ( d -Ala), and meso -diaminopimelic acid (mDAP, with cross-links occurring either between d -Ala and mDAP or two mDAP residues. In E.coli, the d -Ala−mDAP cross-links whose cleavage by specialized endopeptidases is crucial for the expansion of PG predominate.
An ORF of unknown function was identified, YcbK (renamed MepK), as an mDAP−mDAP cross-link that cleaves endopeptidase working in conjunction with other elongation-specific endopeptidases to make space for efficient incorporation of nascent peptidoglycan strands into the sacculus.
In summary, a peptidoglycan hydrolytic enzyme has been identified with a hitherto unknown substrate specificity contributing to the expansion of the peptidoglycan sacculus, which emphasizes the fundamental importance of cross-link cleavage in bacterial peptidoglycan synthesis.
2. Biodegradable solution for hemorrhage – INST, Mohali & NIPER, Hyderabad
This is considered as a breakthrough discovery in the field of the microparticle. A team of Indian researchers led by Dr. Deepa Ghosh from the Institute of Nano Science and Technology (INST), Mohali, have developed this, to lower the severe risks to the health and life of the patient from uncontrolled blood loss following an accident or injury, as hemorrhage can soon turn into a life-threatening situation. The research was conducted in collaboration with the National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad.
Dr. Deepa Ghosh’s team has developed a biodegradable powder that can prevent hemorrhaging. The powder rapidly arrests bleeding and quickens healing, when sprinkled over an injury. Currently, topical hemostats (special materials which can soak up excess fluid and aid in stopping local bleeding) are usually made up of expensive, nondegradable materials.
Some of the previously discovered starch-based hemostats are biodegradable but are slow in absorbing blood & poor in adhering to the injured site. This limits their clinical application. Therefore the research team modified a natural starch compound to convert it into a better performing hemostat. Starting with a biodegradable pharmaceutical excipient ( a type of starch used as the base material in medicines), they tweaked the hydroxyl groups in the compounds to carboxymethyl (CM) groups, which was further converted into a powder form consisting of CM-starch microparticles. After coming in contact with blood, these free-flowing microparticles absorbs the excess fluid within a few seconds and forms a sticky gel-like network. As the gel is biodegradable, it can be left at the wound site without causing toxicity and side effects. This is a breakthrough discovery, therefore it features in Top Research By Indian Bioscientists In 2019
3. Fingernails to test Type-2 diabetes – IIT, Ropar & PGIMER Chandigarh
Type 2 diabetes is the most prevalent form of diabetes in adults in India and across the world, causing glucose accumulation in tissues and organs. Type 2 Diabetes causes severe tissue damage, which is responsible for most of the advanced complications resulting from this disorder. It can even result in the compromised function of key organs including the kidney, heart, skin, bones, & joints. A team of researchers led by Navin Kumar, Indian Institute of Technology (IIT) Ropar, and Sanjay Kumar Bhadada, Post-Graduate Institute of Medical Education & Research (PGIMER), Chandigarh have devised a novel, fast, reliable & cost-effective early diagnostic protocol to quickly and non-invasively assess tissue damage in diabetics thorough evaluation if the quality of the patients’ fingernails.
Tissue integrity maintenance mainly depends on 2 factors – clearing of damaged tissue and repair. In the case of diabetes, high glucose levels cause modification (glycation) of various important proteins like Hb, which makes them bulkier and tougher to get cleared from the cell. This glycated Hb is commonly used to detect diabetes, although it tells us nothing about the extent of tissue damage. The researchers have looked for non-invasive markers for tissue damage and came across keratin, a protein present in skin, hair, and fingernails, which also gets glycated. They tested examined nails from healthy & diabetic individuals for differences in nail surface morphology and roughness, mineral content, material properties, tissue density, disulfide bond content, and protein composition. The study revealed that the extent of glycation was proportional to these changes, as the nail plate quality in diabetic patients was significantly lower than controls.
4. Fighting antibiotic-resistant bugs using Echidna milk – CCMB, Hyderabad
The problem of antibiotic resistance is mounting worldwide, hence it has become very important to identify and test novel drug targets, and also to find potential solutions. Researchers at the Centre for Cellular and Molecular Biology (CCMB), led by Dr. Satish Kumar, have successfully expressed and purified a novel antimicrobial protein from the milk of Echidna, which is an egg-laying mammal native to Australia and New Guinea. These mammals are extensively studied because of their unique position in the evolutionary tree.
The milk protein which was characterized is EchAMP, using a simple E.coli bacterial system. The team artificially introduced the gene for EchAMP into E. coli, acting as a tiny production factory for the protein. They could purify a functional form of the protein in bulk, by altering the sequence of the gene slightly. The purified milk protein from Echidna showed antibacterial activity against both Gram-negative as well as Gram-positive. It could potentially be used in topical applications like ointments or medicated creams for bacterial infections in livestock and humans.
5. Zebrafish in restoring lost vision – IISER Mohali
Zebrafish are the ideal candidates to study possible ways to restore vision following retinal injury, as they have the remarkable ability to regenerate their retinas upon damage. In a recent study, by a group of researchers from the Indian Institute of Science Education and Research (IISER), Mohali, headed by Dr. Rajesh Ramachandran, tried to understand the role played by a group of enzymes called histone deacetylases (HDACs) in Zebrafish retinal regeneration. They have found a new mechanism via which epigenetic factors regulate this process, to restore the vision, especially in vertebrates that have suffered retinal degeneration. HDACs enzymes remove acetyl groups from histone proteins that package and condense DNA in cells, thus modifying them to bind DNA more tightly, preventing gene transcription in that region of DNA. Retina regeneration molecular pathways can be understood by deciphering epigenome modifiers like the HDACs, which may, in turn, lead to the treatment of mammalian retinal damage.
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6. Personalized therapy for Indian gallbladder cancer patients – ACTREC Mumbai
Indian populations observe a high rate of incidence in Gallbladder cancer and a heavy
the mortality rate as well. Dr. Amit Dutt and his team from the Tata Memorial Centre, ACTREC, Mumbai, have identified a pair of genetic mutations in gallbladder cancer patients, which could serve as potential drug targets for cancer treatment. By profiling these mutations in Indian patients, they have pinpointed new genetic therapeutic targets for gallbladder cancer. Conventionally cancer is treated through chemotherapy and radiation. Chemotherapy involves the intravenous administration of a “chemical poison” at a dosage where the cancer cells die, but the patient survives. Along with the cancer cells, the drug ends up killing many normal cells in chemotherapy, reducing the quality of the patient’s life besides the major side effects which include damage to cells in the bone marrow, loss of hair, damage of cells in the digestive tract, mouth, and reproductive system.
Personalized therapy, instead, aims to target the cancerous cells specifically, leaving the normal cells unharmed.
The scientists observed that many EGFR signaling pathway associated genes were mutated or dysregulated in the majority of tumor samples. ERBB2 and KRAS are two such genes showing aberrant expression in tumor cells are. ERBB2 can be inhibited by approved therapeutics used to treat other cancer types. Inhibiting ERBB2 activity in gallbladder tumor cell lines reduced the survival of these cells. But when KRAS was mutated as well along with ERBB2, KRAS mutation rendered the cancer cells resistance to drugs targeting ERBB2 and its downstream signaling. Tumors with additional genomic alterations may lead to patient-specific drugs, and thus, a case can be designed for KRAS mutation profiling of gallbladder cancer patients, allowing clinicians to predict and identify patients whether they are responsive or unresponsive to treatment.
7. Tackling T. gondii infection through suicide mechanism – University of Delhi
Dr. Tanmay Majumdar and his team of researchers from the University of Delhi are introducing a novel way to resist infection by the intracellular parasite Toxoplasma gondii, using a drug that triggers the infected cell’s suicide mechanism, resulting in the death of the parasite residing inside it. T. gondii infections compromise the individual’s immune system and result in loss of vision or severe brain damage. This notorious parasite has the potential to even alter human behavior.
An amino acid, Tryptophan is essential for T. gondii to multiply. But they lack the ability to produce its own tryptophan, hence it depends on the host’s amino acid. T. gondii converts the host’s tryptophan into metabolite melatonin known to enhance cell survival as well as support parasite growth. Thus the host’s immune system is tricked to assume that the cell is healthy and sans infection. But, during a strong immune response, T. gondii converts tryptophan into another metabolite known as kynurenine that can induce cell death, thereby killing itself. scientists added kynurenine to T. gondii infected cells hindering the parasite’s ability to enter cells and activated the host cell’s cell death pathway i.e apoptosis, more of like a metabolite therapy.
8. Molecule to help fight Huntington’s disease – IIT Kanpur
This study features in our Top Research By Indian Bioscientists. Huntington’s disease is a serious neurodegenerative disorder, caused by the abnormal activity of the huntingtin gene. This leads to the build-up of unwanted proteins in brain cells. Some of the symptoms are characterized by uncontrolled movements, depression, & inability to perform locomotor functions like walking, talking and swallowing.
A new study led by Dr. Ashwani Kumar Thakur from the Indian Institute of Technology (IIT), Kanpur has reported a small molecular drug called Arginine Ethyl Ester (AEE) (a derivative of arginine), which shows therapeutic promise against this disease. This molecule exhibits potential in inhibiting huntingtin protein aggregation, i.e the formation of protein clumps or aggregates which are detrimental for the health of neurons.
Huntingtin gene mutation gives rise to a flawed process wherein CAG is replicated excessively, forming extra CAG repeats and thus leading to the formation of long chains of an amino acid called glutamine in the huntingtin protein. These clump together and form a fibrous tangle, which clogs the brain cells and eventually destroys them.
The IIT scientists discovered that arginine- a naturally occurring amino acid, tends to break intermolecular hydrogen bonds which are one of the responsible factors for making aggregates of huntingtin protein through glutamine-glutamine interaction. The team further researched to broaden the scope of availability of therapeutic molecules & found that Arginine Ethyl Ester (AEE) was the most suitable among four such probable candidates, even better at suppressing protein aggregates than arginine itself.
9. The toxic relationship between lead and immunity – Central University of Jharkhand
Lead, a heavy metal, earlier used extensively in paints, gasoline, batteries, plumbing, etc and also made us question the safety of our favorite instant noodles not too long ago, may have damaging effects on the immune system. A new study by Dr. Hena Firdaus and her team of scientists from the Central University of Jharkhand demonstrated that in addition to its many known toxic effects, lead may lower immunity as well. Through a series of experiments on fruit flies, the researchers have discovered a link between lead exposure & susceptibility towards bacterial infections.
In Drosophila melanogaster, hemocytes, play an important role in controlling cellular immunity and immune responses. The researchers found a significant hemocyte count drops when fruit fly larvae were exposed to dietary lead. Many of the flies exposed to high lead concentrations even have a tendency to die prematurely due to bacterial infections.
10. Novel lipid-lowering drug – CDRI, Lucknow
“Genetics loads the gun, lifestyle pulls the trigger”goes a famous saying by a Turkish surgeon. Most of us follow a sedentary and stressful lifestyle, which may be responsible for the rise of lifestyle-related disorders including diabetes, high blood pressure, etc. In a recent study, researchers at the Central Drug Research Institute (CDRI), Lucknow, led by Dr. Amit Gupta and Dr. Anil Saxena, synthesized a class of chemical compounds which have strong anti-oxidant and anti-dyslipidemic activity, thus counteracting the imbalance of lipids, especially cholesterol, in the blood, adding to the arsenal of potential drugs targeting lifestyle disorders like obesity and diabetes.
The researchers synthesized a novel chemical moiety called oxo-propyl indole hydrazone. It has the potential to serve as an excellent lead compound for future drug design efforts. The oxo-propyl indole ring of tryptophan & hydrazone has been used separately as therapeutic options for different metabolic diseases. A single hybrid molecule was synthesized integrating both moieties so that it will possess combined properties. The administration of the synthesized derivatives led to a noticeable reduction in cholesterol level, lipid accumulation as well as blood glucose levels and improvement in lipoprotein lipase activity.
These and many other such, innovations, discoveries and accomplishments are indeed an encouraging reminder that every day, scientists in our country are learning more about how life and the universe works, and how to make it better to live for.
Editor’s Note: Top Research By Indian Bioscientists, Discoveries By India Bioscietists in 2019, Top Indian Bioscientists Research