20-Mar-2020: A key cellular mechanism in Huntington Disease unravelled
Huntington disease (HD) is a progressive genetic disorder affecting the brain that causes uncontrolled movements, impaired coordination of balance and movement, a decline in cognitive abilities, difficulty in concentrating and memory lapses, mood swings and personality changes.
It is caused by a mutation in a gene called HTT. The HTT genes are involved in the production of a protein called huntingtin. They provide the instruction for making the protein. When the genes mutate, they provide faulty instructions leading to production of abnormal huntingtin proteins and these form into clumps. The clumps disrupt the normal functioning of the brain cells, which eventually leads to death of neurons in the brain, resulting in Huntington disease.
While it is known that the clumps formed by the abnormal huntingtin protein disrupt several cellular processes, it is not known whether they also influence the key process in the formation of other proteins in the cell.
A team of scientists from National Centre for Cell Science (NCCS) in Pune led by Dr. Amitabha Majumdar have been working to gain insights into this by studying the HTT gene in fruit flies. They observed that the pathogenic Huntingtin protein causes a decrease in the overall protein production in cells and that the Huntingtin clumps collect together (sequester) molecules of another protein called Orb2, which is involved in the process of protein formation.
They speculated that the Huntingtin clumps were possibly making molecules of Orb2 unavailable to carry out their normal function associated with protein formation, leading to the observed reduction in proteins in the cell. To gain clarity on this, they induced the cells to produce Orb2 in excess, and found that this did indeed reduce the adverse effects of the faulty Huntingtin protein, which supported their speculation.
In humans, a family of proteins called CPEB is equivalent to the Orb2 protein in fruit flies. The scientists conducted further studies and found that CPEB proteins are also sequestered by the pathogenic Huntingtin clumps, similar to the Orb2 protein molecules. This suggests that the insights gained through the studies carried out by this group in fruit flies are relevant to and valuable in understanding HD in humans.
Orb2 protein is also crucial for maintenance of memory in fruit flies. Therefore, sequestration of Orb2 by Huntingtin clumps may hold relevance to the memory-related issues associated with HD as well. The findings of Dr. Majumdar are expected to pave the way for further exploration to understand this disease better.
The research team has published a report on their work in Cellular and Molecular Life Sciences The team included Hiranmay Joag, Vighnesh Ghatpande, Meghal Desai, Maitheli Sarkar, Anshu Raina from NCCS and Mrunalini Shinde, Ruta Chitale, Ankita Deo and Tania Bose from S.P. Pune University.
27-Feb-2020: Diagnostics for Asymptomatic Malaria
The fight against Malaria could get easier with a joint team of scientists from Department of Biotechnology’s Bhubaneswar-based Institute of Life Sciences (ILS) and Bengaluru-based Jigsaw Bio Solutions, coming up with a method that promises to overcome the problem of inadequate identification of asymptomatic carriers of the disease.
Light microscopy and protein immunoassay-based rapid diagnostic tests (RDTs) are used in the diagnosis of Malaria, in mass screening and treatment programs for the diseases, and in surveillance of malaria control measures. They, however, miss out about 30-50% of low-density infections, which typically have less than two parasites/microlitre and are frequently observed in asymptomatic carriers who serve as “silent” reservoirs of the infection capable of transmitting the disease through mosquitoes. Identification of asymptomatic carriers in the endemic areas is recognized as a major hurdle in malaria eradication programmes. New diagnostic methods with higher sensitivity are needed.
In a new study, a team of researchers led by Dr. V. Arun Nagaraj of Institute of Life Sciences and Mr. Srinivasa Raju of Jigsaw Bio Solutions Pvt. Ltd used a new concept of genome mining that identifies identical multi-repeat sequences (IMRS) distributed throughout the malaria parasite genome and successfully targeted them to develop what is called a “ultra-sensitive” qPCR assay for malaria diagnosis.
Validation with clinical samples collected from malaria endemic regions in India showed that that assays were highly sensitive - about 20-100 times more than the traditional methods. They could detect submicroscopic samples. They were four to eight times better than other high-sensitive methods. Further, they were extremely specific for Plasmodium falciparum, which is the deadliest species of malaria parasite and did not cross-react with Plasmodium vivax species, which is the most frequent and widely distributed cause of recurring malaria, but far less virulent.
Speaking to India Science Wire, Dr. Nagaraj said there is a scope to develop multiplexed assays for the simultaneous identification of different species. “Our study could lead to the development of highly sensitive, point-of-care molecular diagnostics that can be explored in miniaturized, isothermal, microfluidic platforms and lab-on-a-chip devices. The IMRS approach can serve as a platform technology for the diagnosis of other infectious diseases as well”.
India has developed a National Framework for eliminating malaria by 2030 and to achieve this goal, identifying the asymptomatic carriers in the endemic areas and clearing their infections are very much important. The new finding could help in this. DBT’s Biotechnology Industry Research Assistance Council funded the project. (Vigyan Samachar)
22-May-2019: Algeria and Argentina certified malaria-free by WHO
Algeria and Argentina have been officially recognized by WHO as malaria-free. The certification is granted when a country proves that it has interrupted indigenous transmission of the disease for at least 3 consecutive years.
Contracted through the bite of an infected mosquito, malaria remains one of the world’s leading killers, with an estimated 219 million cases and over 400 000 malaria-related deaths in 2017. Approximately 60% of fatalities are among children aged under 5 years.
Algeria is the second country in the WHO African Region to be officially recognized as malaria-free, after Mauritius, which was certified in 1973. Argentina is the second country in the WHO Region of the Americas to be certified in 45 years, after Paraguay in June 2018.
Algeria and Argentina reported their last cases of indigenous malaria in 2013 and 2010 respectively.
Over the last decade, improved surveillance allowed for every last case of malaria to be rapidly identified and treated. Importantly, both countries provided free diagnosis and treatment within their borders, ensuring no one was left behind in getting the services they needed to prevent, detect and cure the disease.
French physician Dr Charles Louis Alphonse Laveran discovered the malaria parasite in Algeria in 1880. By the 1960s, malaria had become the country’s primary health challenge, with an estimated 80 000 cases reported each year.
Algeria’s subsequent success in beating the disease can be attributed primarily to a well-trained health workforce, the provision of malaria diagnosis and treatment through universal health care, and a rapid response to disease outbreaks. Together, these factors enabled the country to reach – and maintain – zero malaria cases.
Algeria is where the malaria parasite was first discovered in humans almost a century and a half ago, and that was a significant milestone in responding to the disease,” said Dr Matshidiso Moeti, WHO Regional Director for Africa.
The certificates were presented by the WHO Director-General to representatives from Algeria and Argentina on the sidelines of the 72nd session of the World Health Assembly.
WHO grants a certification of malaria elimination when a country has proven, beyond reasonable doubt, that the chain of indigenous transmission has been interrupted nationwide for at least the previous three consecutive years. In addition, a national surveillance system capable of rapidly detecting and responding to any malaria cases must be operational, together with an effective programme to prevent re-establishment of the disease.
Globally, a total of 38 countries and territories have now been declared malaria-free.
27-Feb-2020: A Rs. 3.6 crore grant to promote research on pigmentary disorder
Studies to understand the problem of pigmentary disorders is expected to get a major shot in the arm with Wellcome Trust/DBT India Alliance conferring an Intermediate Fellowship Award on Dr. Rajender K. Motiani, Assistant Professor at Faridabad-based Regional Centre for Biotechnology. The award consists of a grant of Rs 3.60 crore for a period of five years.
Physiological pigmentation is a critical defense mechanism by which skin is protected against harmful UV radiations. Inefficient pigmentation predisposes to skin cancers, which are one of the leading causes of cancer-associated deaths worldwide. Further, pigmentary disorders (both hypo and hyper pigmentary) are considered a social stigma and therefore they impart long-term psychological trauma and tremendously hamper mental well-being of patients. The current therapeutic strategies are not efficient in alleviating pigmentary disorders.
The research project to be taken up under the award would seek to identify novel targetable molecular players that critically regulate pigmentation process. Further, the researchers would try to repurpose commercially available drugs for treatment of pigmentary disorders. In long run, this project is expected to have a two pronged benefits for society - protection from UV-induced skin cancers and potential treatment options for pigmentary disorders.
So far, the focus in the pigmentation biology field has been to understand the enzymes regulating melanin synthesis and on the melanosome proteins involved in their biogenesis and maturation. However, melanosome biogenesis and melanin synthesis are complex phenomenon and other cellular organelle could potentially regulate this process.
Studies conducted by Dr. Motiani and his team on differentially pigmented melanocytes earlier have indicated that Endoplasmic Reticulum (ER) and Mitochondria are critical regulators of pigmentation. The aim of the new project is to delineate the role of Endoplasmic Reticulum and Mitochondria signaling pathways in pigmentation and to identify the key Endoplasmic Reticulum and Mitochondrial proteins that regulate pigmentation. They would then target these signaling cascades with FDA approved drugs to know whether any known drugs could be repurposed for alleviating pigmentary disorders too. (Vigyan Samachar)