Friday, 7 December 2018

Balancing Act at The Edge of Cells: Study

Study suggests each Cell senses the force and regulates the CLIC/GEEC pathway to maintain membrane homeostasis.

BY SCISOUP DESK


(Left to Right ) Joseph Jose Thottacherry, Prof. Satyajit Mayor and Dr. Mugdha Sathe

We are made up of trillions of cells and they use endocytosis to take up nutrients and growth factors. Endocytosis is a process by which a cell makes small vesicles or bags to take in nutrients from the outside environment. In order to maintain its shape and size, a cell has to maintain the area of its plasma membrane.

Endocytosis decreases the plasma membrane area while the reverse process, exocytosis adds it. A cell needs to balance the two to maintain homeostasis. Imagine removing the membrane bit by bit using endocytosis, the cell will end up shrinking. This means the cell membrane will tense up slowly as the rate of endocytosis is increased. To relieve this tension, the cell needs to lower its endocytosis or increase its exocytosis.

Thus, apart from taking nutrients, endocytosis helps in maintaining the shape and size of the cell.

Now, Prof. Satyajit Mayor’s team has shown how cells regulate this membrane tension using a novel endocytic pathway called the CLIC/GEEC or CG pathway. The study done by lead author Joseph Jose Thottacherry shows that the CG endocytosis is intimately connected to membrane tension by sensing and responding to changes in membrane tension.

“We have shown that increase in endocytosis increases the membrane tension. When we perturb the pathway to decrease endocytosis it decreases the tension. Thus, addition and removal of membrane directly influence the tension of membrane” said Joseph Jose Thottacherry. The results of this study were published in the journal Nature Communications.

Traditionally, endocytosis requires a coat protein to bend the membrane that forms a cage-like structure, and another protein to cut the vesicle. However, the CG pathway, unlike the traditional pathway, works without the coat raising the question, how would a cell bend its membrane for making vesicles?

This was worked out in another published report in Nature Communications  from Prof. Mayor’s lab by lead authors Dr. Mugdha Sathe & Gayatri Muthukrishnan. They found that in the absence of a coat, the cell uses membrane curvature sensing proteins that recognize convex and concave kind of curvatures. They find two proteins called PICK1 (convex) and IRSp53 (concave) that help in vesicle formation by bending the membrane.

Prof. Mayor said, “Our study suggests each cell senses the force and regulates the CLIC/GEEC pathway to maintain membrane homeostasis. If the force goes higher, the CLIC/GEEC pathway is shut down helping the membrane relax while if tension goes lower, endocytosis increases and extra-membrane is taken in.”

So what is this CLIC/GEEC pathway important for? 

Earlier studies have shown that many viruses use this pathway to enter the cells. This pathway is also involved in fruit fly wing development and cell migration. Now, it has been shown that it can help with plasma membrane homeostasis.

Since this pathway is involved in cell migration, it can be involved in spreading of cancer cells to different organs during metastasis or immune cells chasing pathogens. Thus, these two studies are promising and show the importance of understanding non-traditional pathways for their potential translational value.

This study was carried out at National Centre of Biological Sciences (NCBS), Bangalore. The research work was funded by Wellcome Trust-DBT India Alliance and Dept. of Science and Technology (DST), Govt. of India.

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Thursday, 29 November 2018

IISc Seeks To Deliver Clean Water And Sanitation As Part Of An International Initiative

BY SCISOUP DESK

(Dr. Rachel Helliwell, Project Coordinator and a senior research scientist
at the James Hutton Institute, lights a lamp during the inauguration of the project.
Scotland’s Deputy First Minister John Swinney watches on)
Researchers from the Indian Institute of Science (IISc) are collaborating with their counterparts from a consortium led by James Hutton Institute, University of Glasgow and the Ashoka Trust for Research in Ecology and the Environment (ATREE) on a project funded by Scottish Government to deliver a low-cost, decentralized wastewater treatment system.

The pilot facility has been set up in a school – the Berambadi Primary School in the Chamarajanagar district of Karnataka – to serve the needs of its students and staff. It was inaugurated on 28 November 2018 by Scotland’s Deputy First Minister Mr. John Swinney during an official visit to India.

The toilet block at the Berambadi Primary School
At the launch, Mr. Swinney said that it was Scotland’s duty to share its expertise and experience in the area of wastewater treatment with the wider world. Rachel Helliwell, Project Coordinator and a senior research scientist at the James Hutton Institute in Scotland, added that the initiative, which aims to improve public sanitation and environmental health in rural India, drew on the academic and research excellence of scientists from both Scotland and India. Following a screening of a short film tracing its journey, the event saw an interactive session on the lessons learnt from the project and the potential for new partnerships in wastewater treatment.

Lakshminarayana Rao, the lead researcher from IISc, says that the choice of a rural primary school to house the plant was a deliberate one. “Rural schools in India have a mid-day meal scheme. There’s a lot of wastewater coming from the kitchen and handwash. This is a low-hanging fruit because this water can be recycled to be used in toilets for flushing,” he explains.

Most wastewater we generate is called grey water (wastewater that does not originate in toilets). By contrast, wastewater which contains faeces and urine, and therefore pathogens, is referred to as black water.

To recover grey water, the Berambadi project uses, among other methods, plasma technology developed by Rao’s team at IISc. “We’re using a component of plasma to generate ozone which disinfects the water,” he elaborates. His lab has developed a high-throughput ozonator which provides large volumes of ozone while ensuring that its energy demands are lesser than conventional technologies.

On the other hand, black water is treated before it is discharged by a multi-step anaerobic digestion process developed by the Scottish water scientists. This ensures that neither the groundwater nor the river downstream is contaminated.

Besides grey water recovery and black water treatment, the project also has a rainwater harvesting system which collects about 60,000 litres of water during the rainy season for use by the school. In addition, it has an incinerator to help dispose sanitary napkins. The entire system – as well as lighting for the school – is powered by solar energy, which Rao says makes it a “stand-alone, grid-independent system.”

A critical feature of the project, which began over a year-and-a-half ago, has been its engagement with the local community. It has been designed keeping in mind the local socio-cultural and economic conditions as well as sanitation behaviours. “This initiative is hugely exciting because it integrates social science and new technologies to deliver on an ambitious and important Sustainable Development Goal: providing clean water and sanitation for all by 2030,” says Helliwell.

Rao believes that this modular system can be replicated as well as scaled up. He says that these decentralised plants can also be built in urban settings like apartment complexes and educational institutions, especially those with hostels. According to him, by merely combining a grey water recovery system with a rainwater harvesting plant, the use of fresh water – which he describes as a luxury for a country like India – could go down by as much as forty percent.

Wednesday, 14 November 2018

NIPGR Researchers Open A Window On The Secrets Of Plant Life to Public

NIPGR organized an Open day for the general public in order to popularize research in plant sciences and its applications.

BY SCISOUP  Appeared In BiotechTimes ResearchStash


On October 26, 2018, New Delhi based National Institute of Plant Genome Research (NIPGR), an autonomous institute under the Department of Biotechnology, Government of India, had organized an Open day for the general public in order to popularize research in plant sciences and its applications.

Students and teachers were invited from various National Capital Region (NCR) based schools and colleges to visit laboratories of NIPGR. Here is a link to a short report on NIPGR Science Outreach event: https://www.youtube.com/watch?v=wL-BYlJERag
 
In this event, a total of 1079 students participated along with their teachers. Among the participant, 958 were school students from 30 different government and private schools and 121 college students from 3 colleges. The NIPGR community presented 31 posters and 18 exhibits on various aspects of life sciences in general and plant sciences in particular.


“The open day is an opportunity for NIPGR to open its doors to the local community and contribute towards inculcating in students a passion for science,” said Prof. Ramesh V. Sonti, Director at NIPGR, New Delhi.

NIPGR scientists, technical specialists, and young researchers explained in very simple language about ongoing plant research activities in the institute. They covered various aspects of plant sciences including photosynthesis, ecological nitrogen fixation, plant-pathogen interactions, crop yield improvement etc.

Various posters, exhibitions, and practical demonstrations like how to isolate DNA from plants, how to visualize protein and DNA in gel etc. were arranged to provide real experiences of a working molecular biology laboratory. The visitors were also provided a tour of the research facilities at NIPGR, where they were explained about the working of various scientific instruments like the Confocal Microscope, automated DNA Sequencer, PCR, Real-time PCR, central instrumentation facility etc.

School students got an opportunity to witness the banana plant tissue culture techniques for a better understanding of working with plants in the laboratory. Students were also shown plant cells under the foldscope microscope. They were shown videos clearly demonstrating how plant stem cells look like under advanced microscopes.

Day-Long activities and interactions with NIPGR researchers have sensitized and inspired students and teachers about the opportunities in plant sciences, particularly in plant molecular biology.

Monday, 22 October 2018

Injectable Gel May Deliver Islet Cells for Type 1 Diabetes: Study

IIT-Guwahati researchers developed an injectable gel using silk proteins to deliver insulin-producing cells needed to address type-1 diabetes.

By Ratneshwar Thakur Published in India Science Wire


(Left to Right) Dr. Biman B. Mandal And Dr. Manishekhar Kumar


Researchers at the Indian Institute of Technology, Guwahati have developed an injectable gel using silk proteins to deliver insulin-producing cells needed to address type1 diabetes.
The gel has been tested in rats. Normally islets in the pancreas are surrounded by the extracellular matrix which provides structural and biochemical support to cells. The components of this matrix bind to transmembrane proteins on the islet surface to facilitate cell to cell connection, proliferation and insulin secretion.
Previous studies had suggested hydrogels have potential to deliver islets as they contain high water content and mimic hydrophilic content of extracellular matrix. However, use of harsh chemicals in making gels makes them unsuitable to deliver cells or bioactive molecules.
To address this problem, researchers used mixture of two silk proteins (mulberry Bombyx mori and non-mulberry Antheraea assama) which leads to self-gelation. Insulin-producing islet cells were harvested from rats and encapsulated in the hydrogel. The hydrogel was loaded with immunosuppressive drugs to prevent immune rejection. It was then injected under the skin of rats.
“The islet delivery matrix could be easily injected in a minimally invasive manner while maintaining islet cell viability and glucose-responsive insulin production at the transplantation site. The hydrogel could be highly affordable as raw materials for making the hydrogel are abundantly available,” said Dr. Biman B. Mandal, who led the research.
The development, he said, is promising as it may help type 1 diabetes patients to get rid of frequent insulin injections in future.
The research team included Manishekhar Kumar, Prerak Gupta, Sohenii Bhattacharjee and Biman B. Mandal (IIT- Guwahati); AND Samit K. Nandi (West Bengal University of Animal and Fishery Sciences, Kolkata). The study results have been published in journal Biomaterials.

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Friday, 19 October 2018

This Gel Can Protect Farmers From Toxic Pesticides

Indian farmers usually do not wear any protective gear while spraying chemicals in farms. This exposes them to harmful toxins contained in pesticides, causing severe health impacts and even death in extreme cases. Indian scientists now develop a protective gel to address this problem. 

By Dinesh C Sharma Published in India Science Wire
(Members of the research team at InStem, Bangalore)

Indian farmers usually do not wear any protective gear while spraying chemicals in fields. This exposes them to harmful toxics contained in pesticides, causing severe health impacts and even death in extreme cases. Indian scientists have now developed a protective gel to address this problem.

The gel can be applied on skin and can break down toxic chemicals in pesticides, insecticides and fungicides including the most hazardous and widely used organo phosphorous compounds. The gel deactivates these chemicals, preventing them from going deep into the skin and organs like the brain and the lungs. It has been found to be effective in tests done in rats and researchers hope to soon test it in humans.

Exposure to chemicals contained in pesticides interferes with an enzyme called acetylcholinesterase (AChE) which is present in the nervous system and is critical for neuromuscular functions. When its functioning is disrupted by chemical pesticides entering the body through the skin, it can cause neurotoxicity, cognitive dysfunction and even death in severe cases. 

When the gel was applied on rats and they were exposed to a lethal dose of pesticide MPT, it did not lead to any change in their AChE level, showing it could prevent penetration of the pesticide into the skin.

The gel, named poly-Oxime, has been prepared by researchers at the Institute for Stem Cell Science and Regenerative Medicine (InStem), Bangalore from a nucleophilic polymer. In lab studies, rats treated with poly-Oxime gel survived pesticide treatment, whereas rats with no gel or sham gel showed symptoms of poisoning or died. The results of the study were reported in journal Science Advances on Thursday.

The gel does not act like a physical barrier, but it acts like a catalyst to deactivate organophosphate. An oxime could hydrolyze multiple organophosphate molecules, one after another. And it can do so at temperatures ranging from 20 to 40 degrees, and even after long exposure to ultraviolet light. 

“Our data suggests that a thin layer of poly-Oxime gel can hydrolyze organo-phosphates on the skin; therefore, it can prevent AChE inhibition quantitatively in blood and in all internal organs such as brain, lung, liver, and heart,” the study notes. It has also been found that the catalytic gel can work against a range of commonly used commercial pesticides, insecticides, and fungicides.

“At present, we are conducting extensive safety studies in animals which will be completed in four months. Subsequently we plan a pilot study in humans to demonstrate efficacy of the gel,” Praveen Kumar Vemula, a senior member of the research team, told India Science Wire.

As the next logical step, the research group plans to develop an active mask to deactivate pesticides since the gel now developed does not provide any protection from inhalation of pesticide vapours, according to Vemula.

In order to understand the problem of toxicity caused by pesticides, researchers interacted with several farmers and their families. While many of them said they experienced pain right after spraying pesticides, they had no access to protective means. Farmers, according to researchers, showed willingness to adopt any low-cost topical methods that can prevent pesticide exposure.

The research team included Ketan Thorat, Subhashini Pandey, Sandeep Chandrashekharappa, Nikitha Vavilthota, Ankita A. Hiwale, Purna Shah, Sneha Sreekumar, Shubhangi Upadhyay, Tenzin Phuntsok, Manohar Mahato, Kiran K. Mudnakudu-Nagaraju, Omprakash Sunnapu and Praveen K. Vemula.

Tuesday, 16 October 2018

Scientists Find Why Long Chain Lipids Accumulate Inside Brain In PHARC Disorder

Study will help to better understand the pathology of PHARC and it might enable development of much-needed biomarkers, very long chain lipids, for better diagnostics.



(Research team at IISER Pune)

PHARC is a rare genetic human neurological disorder caused by mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. 

Recent studies have shown that mice without ABHD12, murine model of PHARC, show increased concentrations of lyso-phosphatidylserine (lyso-PS) lipids in brains. Now Indian researchers, using mice model, have found the biochemical explanation for such very long chain lipids accumulation in the brain.

Dr. Siddhesh S. Kamat’s team at Indian Institute of Science Education and Research (IISER), Pune - have shown that the enzyme ABHD12 has a strong substrate preference for very long chain lipids which contains ≥ C22 atoms. 

Researchers found the location of this enzyme (ABHD12) in the membrane of the endoplasmic reticulum, a cellular compartment, where virtually, all of the very long chain lipids are biosynthesized. The results of this study were published in ‘The Journal of Biological Chemistry.’

“We first chemically synthesized a library of lipid substrates ranging from fatty acids C10 – C24 with different degrees of un-saturations. Next, we performed enzyme kinetics studies for this lipid library against recombinant human, and endogenous mouse brain ABHD12, and found in both cases that there is a preference for very long chain lipids,” said  Dr. Siddhesh S. Kamat.

“Our study will help to better understand the pathology of PHARC and it might enable development of much-needed biomarkers (very long chain lipids) for better diagnostics for this condition,” he added.

“This work is a classic illustration of the value of a biochemical approach in understanding what a clinically important protein actually does in cells. This biochemical characterization reveals a very broad substrate choice for this important protein, and also explains how cells can maintain an appropriate balance of long-chain lipid substrates. This can now be used to identify activators or inhibitors of this enzyme,” commented Dr. Sunil Laxman from InStem, Bangalore, who was not associated with this study.

The research team included Alaumy Joshi, Minhaj Shaikh, Shubham Singh, Abinaya Rajendran, Amol Mhetre and Siddhesh S. Kamat from IISER Pune. This study was supported by Wellcome Trust DBT India Alliance and DST-FIST infrastructure development grant.

Journal Reference:

Monday, 1 October 2018

Scientists Open New Avenue To Study Head Muscle Dystrophy

The study, done in mice and human stem cells, may help in future to test drugs developed for treating muscular dystrophies involving head muscles.


                                                     Dr. Ramkumar Sambasivan with his research team at inSTEM


Indian researchers have identified the mechanism by which muscles above the neck, known as head muscles, are formed during development of the embryo in the womb.

The study, done in mice and human stem cells, may help in future to test drugs developed for treating muscular dystrophies involving head muscles.

Till now scientists had only known about the way muscles below the neck develop in the embryo. The new study has found that the process is different for the development of head muscles. It was observed that formation of head muscles was triggered by inhibition of two pathways called Wnt/beta-catenin and Nodal pathways, while muscles below neck require switching on of two different pathways (Wnt and Fgf).

“We found that muscles in the head, such as jaw and facial muscles, have fundamentally different developmental program when compared to that of muscles below neck. We have shown this by mutating two genes in mice embryos,” explained Dr. Ramkumar Sambasivan, study leader and Scientist at the Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bangalore.

“We observed that in the mutant mice embryos, muscle development below neck fails completely. The head muscle development, however, surprisingly, appeared completely normal. These findings provided evidence that the two muscle groups have distinct paths of development,” he added. 

“The study has traced an evolutionary process that allowed emergence of head in vertebrates and identifies mechanistic cues that might be involved in the process. This information can be used to streamline therapy for muscular disorders affecting distinct parts of the body, rather than a ‘one therapy fits all muscles’ approach,” commented Dr. Suchitra Gopinath of Translational Health Science and Technology Institute (THSTI), Faridabad, who was not part of this study.

Sam J. Mathew, Assistant Professor at Regional Centre for Biotechnology (RCB), Faridabad, said, “This work raises interesting possibilities to find new treatment strategies for patients who have weakness and dysfunction of the head muscles.”

The research team included Nitya Nandkishore (InStem and SASTRA University, Thanjavur), Bhakti Vyas (InStem and Manipal Academy of Higher Education, Manipal), Alok Javali (InStem and NCBS), Subho Ghosh and Dr. Sambasivan (InStem). 

The results have been published in journal DevelopmentThe study was supported by Department of Biotechnology.

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Friday, 21 September 2018

NBRC Scientists Unravel Mysteries of Human Brain In An Open Day To Lay Public

DBT-National Brain Research Centre (NBRC) organized an Open Day  to educate the general public about scientific research and its benefits.




In order to educate the general public about scientific research and its benefits, DBT-National Brain Research Centre (NBRC), Manesar - organized an Open Day on September 20, 2018, under India International Science Festival 2018 (IISF) banner. Students and teachers were invited from schools and colleges to visit laboratories of NBRC. 

Scientists of NBRC arranged poster sessions to showcase their ongoing neuroscience research activities. The posters were explained in easy language by young researchers. In addition to more than a dozen posters, a talk was delivered by a senior scientist Prof. Shiv K. Sharma on functioning of the healthy brain and how diseases affect the brain. 

He explained, how brain forms memories and helps in recalling them. Prof. Sharma also explained experiments that are commonly done to understand the mechanisms of learning and memory. 

“The enthusiasm of students in Science in general and in brain and Neuroscience in particular was evident from their keen interest in the lecture, and the questions that followed. Interaction with teachers, and answering their queries was a full-filing experience. The activities organized by NBRC were appreciated by the teachers and the students alike,” said Prof. Shiv Kumar Sharma. 

The visiting students were also provided a tour of research facilities at NBRC, where they got a chance to see how imaging of human brains is done by MRI and EEG. Live demonstrations of EEG recordings were done and students enthusiastically participated in the activity. 

“It was a wonderful experience to discuss our discoveries on brain infections with college and school students. We look forward for another opportunity to interact with young minds,” said Prof. Pankaj Seth. 

All students were given demonstration of real human brain and spinal cord for a better understanding of the nervous system which was liked by all the students. Students were also shown human brain stem cells under the microscope and were educated on this exciting and upcoming field of stem cells. They were shown videos taken using microscopes that clearly demonstrated how neural stem cells divide under culture conditions. 

The day long activity ended with interaction of students with researchers at NBRC. Students enjoyed their visit and wanted to know when will be next Open Day so that they can come back and learn more about human brain and how researchers unravel the mysteries of human brain. 

Prof. Neeraj Jain, Director, NBRC, informed that the next Open Day will be on December 17, 2018.

Wednesday, 19 September 2018

Experiments In Rats Show Some Bad Memories Can Be Forgotten

Indian scientists found that exaggerated response and difficulty to get rid of bad memories could depend on whether the bad memory was formed before or after a stressful event.


Prof. Sumantra Chattarji and Dr. M. M. Rahman (Left to Right)


It is believed that exaggerated response to bad memories is similar for all negative memories. Now, a team of Indian scientists have shown that exaggerated response and difficulty to get rid of bad memories could depend on whether the bad memory was formed before or after a stressful event.

The finding is based on experiments done in rats using a technique called fear conditioning. When a rat is presented with a sound tone along with an aversive cue, it forms a memory that the tone is bad. The rat freezes in fear whenever the tone is played. But when the tone is repeated without the aversive cue, the animal learns to forget aversive memory and realises that the tone is not bad.

When rats underwent stressful experience before fear conditioning, they showed increased fear response and inability to forget aversive memory. In contrast, when they underwent the stressful experience afterwards, they did not show any enhanced response fear or inability to extinguish the fear memory.

Researchers also recorded brain activity of the rats as they underwent fear conditioning and stressful experience. It was found that although amygdala (emotional hub of the brain) remained hyperactive in stressed animals, it did not affect expression of fear memory. The prefrontal cortex which remained relatively unaffected in stressed animals seemed to control the normal fear response.

Earlier studies had shown that amygdala and prefrontal cortex play important role in fear-related behaviour. While amygdala is involved in formation of fear memories, prefrontal cortex (involved in making executive decisions) helps in their regulation and finally extinction. Stress has been found to elicit opposite effects on the two brain structures.

“When fear-enhancing effects of prior exposure to stress are not in play, the expression of fear reflects normal regulation of prefrontal activity, not stress-induced hyperactivity in the amygdala,” explained Prof. Sumantra Chattarji, leader of the research team.

Stress-induced strengthening of fear memories and impaired fear extinction are generally believed to be behavioural manifestation of these contrasting effects on amygdala and prefrontal cortex. This has given rise to the view that stress impairs the ability to extinguish fear memories. “Our study questions this view”, researchers said. However, more studies in animals and humans will be required to further explore how this research can be used for treating stress disorders.

The study done by Bangalore-based National Centre for Biological Sciences (NCBS) and Institute for Stem Cell Biology and Regenerative Medicine (inSTEM) has been published in journal eLife. The research team included Mohammed Mostafizur Rahman, Ashutosh Shukla and Sumantra Chattarji. This work was supported by Department of Atomic Energy and Department of Biotechnology, Govt. of India.


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Friday, 14 September 2018

New Approach Can Help Make Better Titanium Alloy For Implants

A new approach for developing orthopedic implants with better ability to bond with the bone.


                                                                                           Kaushik Chatterjee and Sumit Bahl (Left to Right)

Researchers at the Indian Institute of Science (IISc) in Bangalore have proposed a new approach for developing orthopedic implants with better ability to bond with the bone.


Currently, orthopedic implants for knee and hip arthroplasty are made of metallic alloys that contain potentially toxic elements like aluminum, vanadium and nickel. They are also much stiffer than human bone and don’t bond well with the bone.

The research team at IISc has developed a strategy to increase the bioactivity of titanium alloy consisting of non-toxic elements - titanium, niobium and tin, through surface severe plastic deformation (metal working techniques). This approach could help produce new titanium alloys that are less stiff compared to currently used. The researchers have published a report on their work in the journal ‘ACS Biomaterials Science & Engineering.’

The researchers used a technique known as surface mechanical attrition treatment (SMAT) to boost bioactivity of alloy’s surface. In this technique, the metal alloy sheet is placed inside a chamber containing hard steel balls typically used in ball bearings. The chamber is vibrated using electromechanical means because of which the balls start to move randomly at high speed inside the chamber.

“The SMAT treatment deforms surface of the metal sheet, which leads to increase in surface hardness, modification in surface roughness and surface wettability and its chemistry. These modifications are responsible for increasing biological activity of the metal,” explained Dr Kaushik Chatterjee, who led the research, while speaking to India Science Wire.

SMAT can improve biomechanical properties like fatigue and wear resistance, added Dr Sumit Bahl, lead author of the study. The equipment used for the experiment was developed in collaboration with a Bengaluru company.

"The study has shown that traditional metal processing techniques can be still used to improve the cell-material interaction of new class of titanium alloys," commented Dr T.S. Sampath Kumar of Indian Institute of Technology, Madras, who was not connected with the study.

The research team included Sai Rama Krishna Meka, Sumit Bahl, Satyam Suwas, and Kaushik Chatterjee. The study was supported by the Science and Engineering Research Board (SERB).

Thursday, 6 September 2018

Scientists Find Protein Role In Muscle Disease

A new study has shown that genetic loss of SIL1 disrupts Endoplasmic Reticulum (ER) homeostasis, leading to a condition of muscle disease.



Linda M. Hendershot and Viraj P. Ichhaporia (Left to Right)

Marinesco-Sjögren Syndrome (MSS) is a rare pediatric disease, where patients experience loss of balance and coordination, develop cataracts, and undergo severe and progressive loss of muscle strength. Scientists have previously shown a link between mutations in the SIL1 gene and MSS. However, it is not well understood how loss of SIL1, as in the case of MSS, causes the manifold signs of this disease.

A research team led by Dr. Linda M. Hendershot and Viraj P. Ichhaporia at St. Jude Children’s Research Hospital, USA, has recently shown that the genetic loss of SIL1 disrupts Endoplasmic Reticulum (ER) homeostasis, leading to a condition of muscle disease. The results of this study were published in the journal ‘Disease Models & Mechanisms’.

The ER, a network of membranous tubules within the cytoplasm of a eukaryotic cell, folds and modifies newly formed proteins so they have particular 3-dimensional shape. SIL1 plays a key role in the process of protein folding where a newly synthesized string of amino acids gets transformed to its respective 3-dimensional shape to perform its functions.

“We use a preclinical model that is lacking SIL1 to help us better understand the underlying disease mechanisms of MSS. We focused on the progressive loss of muscle mass, which is a hallmark of MSS, and accompanying muscle weakness. We reasoned that understanding the molecular changes leading to muscle dysfunction would provide insights into many other pathological aspects of MSS,” said the lead author, Viraj P. Ichhaporia. 

“We observed that as the preclinical model began to age, they had difficulty holding on to the wired food tray while eating. This observation paved the way for the first experiment, which proved that the preclinical SIL1-deficient disease model displayed significant muscle weakness, and urged us to further investigate the underlying mechanisms” he added. 

Dr. Linda Hendershot, the corresponding author of this study, stated “we show that loss of SIL1 affects protein folding within the cell and dramatically disrupts protein homeostasis, which causes a cascading ripple effect.” 

“This research is particularly exciting to our lab because we are now able to understand the molecular events underlying muscle weakness in the preclinical model lacking SIL1, and believe that a similar ripple effect could also trigger the collapse of protein homeostasis in individuals with MSS. Identifying the molecular milestones of the progressive loss of muscle mass and strength that we can monitor, it allows us to ask how we can treat these defects?,” she concluded.

The research team included Viraj P. Ichhaporia, Jieun Kim, Kanisha Kavdia, Peter Vogel, Linda Horner, Sharon Frase and Linda M. Hendershot. The study was funded by the National Institue of Health and the American Lebanese Syrian Associated Charities at St. Jude Children’s Research Hospital.

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