Design for a framework for the Urban Water System management proposal submitted.
As an editorial designer, its not always that one comes across exciting projects. But when that project comes along, invariably there is holiday I would have planned half a year ago and it overlaps the deadline or some other commitment comes in at the same time. There are so many times I have looked back at such projects and wondered if I would have done a better job if I had more time. And most times the answer is yes. But there was one project which I did my best. I had an amazing illustrator to work with and an excellent editor as my team mate. And this was a brochure for the Ecological Sciences department of Indian Institute of Science, Bangalore, India. The team and the content was the best I could as for (in a long time) and that made my life easier. The design that came out of the whole team speaks for it.
INTERNATIONAL CONFERENCE ON BRAIN DISORDERS & TREATMENTS
16-18 November 2015
Faculty Hall, Indian Institute of Science Bangalore
What is dementia and how is it caused?
The underlying genetic bases of Alzheimer’s disease
Can we prevent the onset of dementia in Alzheimer’s disease?
These are some of the key areas that will come under the lens at the international conference: “Neurodegenerative Diseases: Pathogenesis to Therapy” conference, which will be held between 16-18 November 2015 at the Faculty Hall, Indian Institute of Science, Bangalore. The conference is being organised by the Centre for Brain Research, an autonomous centre at the IISc. Scientists from various national and international research institutes and Universities will present their studies and findings during these three days and explore novel therapies. The main focus will be on neurological disorders related to age: their causes, mitigation and possible treatments.
Dementia refers to a range of symptoms that includes the loss of memory and decline in mental abilities like thinking, problem solving and language, caused due to brain degeneration. It is a common symptom of Alzheimer’s disease (AD) and has been noted in people in their mid-60s. Research suggests the onset of dementia could be delayed, and that there are treatments for the symptoms of the disease which can slow down the progression of dementia.
The degeneration of the brain as we age is primarily a medical problem. But, with the increasing ageing population across the world, it has now become an economic issue also. “Age related neurological disorders have been a cause for public health concern in developed countries. In the near future, India and China will see the largest increase in new cases of dementia. So, there is growing global concern about ageing disorders, in general and dementia, in particular”, said Professor Vijayalakshmi Ravindranath, chairman, Centre for Neuroscience, IISc, Bangalore.
The first day of the conference will focus on Alzheimer disease- its causes, symptoms and possible therapy of its primary symptom – dementia. The day’s talks include
- John C. Morris, a lifetime achievement award winner from the Alzheimer’s Association for his contributions to this field, currently at the Washington University School of Medicine will speak about delaying the onset of dementia in AD and the ongoing trials.
- Yves Joanette, University of Montreal, Canada, will talk about the challenge that dementia poses and the collaborative efforts at a global level to understand the origins of the diseases causing dementia.
- Arthur Toga, founder of the Laboratory of NeuroImaging, University of California, Los Angeles, describing his work on making data from various laboratories accessible, and using a wide range of instruments and different protocols, to discover meaningful patterns.
- Sudha Seshadri from Boston University School of Medicine, will present the genetic aspect of Alzheimer disease research.
- The possible links between Dementia and type 2 diabetes will be discussed by Prof. Velandai Srikanth, a geriatrician at the Monash medical centre, Monash University, Melbourne.
- Suvarna Alladi, Nizam Institute of medical Sciences, Hyderabad, will address the possible role of multilingualism in the delay of onset of dementia.
- Mary Ganguli, University of Pittsburgh will speak about the relationship of brain’s function and dysfunction to the overall population as opposed to an individual.
- Murali Krishna will present his research from populations of Mysore and how nutrition and growth in early life and socio-economic adversities affect cognition in individuals.
The second day will be a range of topics on factors and mitigation of neurodegeneration due to age, how lifestyle factors and other diseases can influence brain damage owing to AD, Parkinson, Lafora disease or Amylotrophic Lateral Sclerosis. Dr. Ana Ines Ansaldo from University of Montreal, Canada, will talk about mitigation of neurodegenerative symptoms. Dr. Rosalyn Moran from Virginia Tech Carilion Research Institute, will present a mathematical predictive model to examine the impact of life experiences in aging neurobiology. Dr. Stanley Fahn, Columbia University Medical centre, followed by Dr. Uday Muthane’s, (Parkinson aging and research foundation, Bangalore) talk on Parkinson’s disease and mitigation probabilities.
The last day will be a presentation by Dr. Sangram Sisodia from University of Chicago, on genetic mutations causing Alzheimer followed by Dr. M. M. Panicker’s (NCBS, Bangalore) research on stem cell modelling on late onset of the disease. Prof. Colin Masters, University of Melbourne, will speak on possible gene therapy in Alzheimers before the concluding session of the conference – a panel discussion on dementia.
16-18 November 2015
Faculty Hall, Indian Institute of Science Bangalore
“By 2050, more than 50% of the ageing population will be in South East Asia”, said Prof Yves Joanette, during the first session of the International Conference ‘Neurodegenerative Diseases: Pathogenesis to Therapy’ at the IISc today. “Globally, about 30% of the population would be 60+ very soon”, she added.
This immediately implies an increase in incidence of dementia. With an increasing aged population, dementia is becoming more of an economic problem, rather than a medical problem.
“India will contribute to dementia research both within the country and globally”, said Joanette, pointing out to the Rs 225 crore grant provided by Kris Gopalakrishnan to IISc. During his speech at the inauguration, Gopalakrishnan said “Understanding the human brain would help us improve the condition of people whose lives are affected by these diseases. There is a huge avenue for computational research, where India can really provide inputs”.
Dementia refers to a range of symptoms that includes the loss of memory and decline in mental abilities like thinking, problem solving and language, caused due to brain degeneration. It is a common symptom of Alzheimer’s disease (AD) and has been noted in people in their mid-60s. Dementia is also caused by other factors, said Joanette. “We need to examine the cascade of events that end up in dementia”, she said.
“We also need to find ways to deal with dementia-affected population – their quality of life and strengthening services for caregivers and families”, she added.
AD, first diagnosed in 1906, is a disease where neurons in the brain die and the brain wastes away as a result. Dr John Morris from the Washington University in St Louis called it a ‘global epidemic’. “The first stage of the disease is generally silent, and cannot be detected by current diagnosis methods”, he said. “The second phase is characterised by dementia and cognitive impairment. We currently have no therapy for the underlying cause of AD – the neuronal degeneration”, he added.
“We need population level studies to complement clinical ones”, said Dr Mary Ganguli from the University of Pittsburgh. Human beings are hetergenous subjects, not uniform like lab rats, she said. “It is crucial to examine the external factors from the population around a patient. Such data is lacking from countries like India”.
Ganguli has developed an India-specific questionnaire which can be used for population level dementia surveys. Neuro-physiological tests, the usual norm for diagnosis, were not feasible with illiterate people. She found an incidence of 1.17% in a population in Haryana, as opposed to 8% at a locality in the US. “The study needs to be expanded to other socio-economic classes, and across the country”, she said.
Dr Sudha Seshadri, an alumnus of CMC Vellore who is now at Boston University, has been “looking at new genes or new targets for understanding the biology of AD, which would help discover new drugs and therapeutic approaches”. She suggested genome-wide surveys to look at possible targets for gene therapy.
Murali Krishna, an Early Career Wellcome Trust-DBT fellow from Mysore, examined the hypothesis that a smaller birth weight, because of a smaller head, increases chances of dementia when the person ages. Examining more than 1000 people born in a particular hospital in Mysore, he was able to establish that low birth weight, combined with low socio-economic status, increased the prevalence of dementia and cardiometabolic disorders.
Suvarna Alladi of Nizam’s Institute of Medical Sciences, Hyderabad, said that India was ideal to test the hypothesis of whether speaking more than one language maintains cognitive functions better. “Switching between languages maintains higher cognitive functioning”, she said. “Irrespective of literacy, being multi-lingual helps to delay dementia. Illiterate but skilled workers like artisans, potters and weavers had heightened cognitive abilities and hence late onset of dementia”, she added.
Prof. John C. Morris http://neuro.wustl.edu/aboutus/facultybiographies/morris
Murali Krishna http://wellcomedbt.org/fellowsprofile/dr-murali-krishna-125
17 November 2015
Faculty Hall, Indian Institute of Science Bangalore
“Sitting is the new smoking. Eight hours of sitting does similar damage to what smoking does to you”, said Manjari Tripathi, a Professor of Neurology at the All India Institute of Medical Sciences, New Delhi. Life expectancy in India has shot up in the last 50 years, thanks to better medical facilities.
“Soon, India will have the third largest ageing population following the US and China”, she said. “One in six women beyond 55 are likely to develop dementia. However, the factors leading to dementia are still an enigma”. Tripathi has initiated a study that will monitor the health of a rural and an urban group, over the next couple of decades.
Dementia refers to a range of symptoms that includes the loss of memory and decline in mental abilities like thinking, problem solving and language, caused due to brain degeneration. It is a common symptom of Alzheimer’s disease (AD) and has been noted in people in their mid-60s.
Can we remodel the brain after it has aged? At a very interesting talk during the second day of the International Conference ‘Neurodegenerative Diseases: Pathogenesis to Therapy’ at the IISc today, Ana Ines Ansaldo from the University of Montreal discussed brain remodelling as a therapy for Alzheimer’s Disease.
The brain is capable of some degree of plasticity, or remodelling. With age, this ability typically decreases. Ansaldo has found that engaging the brain in novel, complex tasks provides it with an ‘enriched environment’ that delays onset of brain degeneration. Therapy induced plasticity can potentially prove beneficial for Alzheimer’s patients, her research has shown.
Stanley Fahn from Columbia University spoke on the symptoms and pathogenesis of Parkinson’s Disease. The disease is caused due to degeneration of neurons, and it progresses slowly in most people; the person’s brain slowly stops producing dopamine, a neurotransmitter – a chemical used to communicate between neurons. Hirsch Etienne from the Brain and spine institute, Paris, spoke on the unmet therapeutic needs in Parkinson’s disease. K P Mohan Kumar spoke on the specific protein Prohibitin and its relation with Parkinson’s.
Jean-Pierre Julien from Laval university, Canada, spoke on possible therapies for the disease Amylotrophic Lateral Sclerosis (ALS). The disease affects motor neurons, the brain and spinal cord, causing muscle weakness and paralysis.
Rosalyn Moran from Virginia Tech spoke about her research on the mathematical modelling of the brain, which can help predict long term ageing patterns and propensity for disease.
Ana Ines Ansaldo: http://www.laboansaldo.com/ana_ines_e.html
18 November 2015
Faculty Hall, Indian Institute of Science Bangalore
The last day of the International Conference ‘Neurodegenerative Diseases: Pathogenesis to Therapy’ was packed with discussions regarding the latest research about Alzheimer’s and dementia, especially detection and therapy.
A panel discussion in the afternoon discussed the Dementia Network – designed to improve the system of care for individuals with Alzheimer’s Disease and dementia. Stanley Fahn from Columbia University stressed the need for collaboration among institutes, and among different streams – doctors, nurses, academicians, caregivers and families of affected people. Such a network can be used to establish common protocols and assessments for diagnosis, treatment and data collection.
Sangram Sisodia from the University of Chicago stressed the need for scientists to network together and use technology to the best possible extent. Yves Joanette from the University of Montreal stressed on the need for Big Data; and the need for large international collaborations to generate Big Data. Narahari from IISc stressed further on the need for complex algorithms that can handle the kind of data needed to understand neurological diseases. He spoke of the need to complement crowdsourced data with expert data, to get a good picture.
Upinder Bhalla from the National Centre for Biological Sciences said that the Centre for Brain Research established at IISc was an excellent starting point to setup the Dementia Network in India. Mathew Varghese from NIMHANS also stressed the same – when setting up the network was discussed 6 years ago, he said “research into Alzheimer’s Disease was in its infancy”.
In other talks, Sisodia from the University of Chicago has been working on the function of presenilin, a protein that is involved in the generation of beta-amyloid, which accumulates to form the ‘amyloid plaques’ typical of Alzheimer’s Disease. Deepak Nair from the Centre for Neurosciences, IISc has been studying the Amyloid Precursor Protein, which generates the beta-amyloid that leads to plaques. Vijayalakshmi Ravindranath studies how the plaques accumulate.
Balaji Jayaprakash from the Centre for Neurosciences, IISc has been studying mice affected by Alzheimer’s Disease to test memory and how it disappears with time.
Using laboratory strains of patient cells, Mitradas Panicker from the National Centre for Biological Sciences has developed a ‘gene map’ of the neural cells, which can help in earmarking the genes responsible for Alzheimer’s Disease.
Prof. John Morris is the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology, Professor of Pathology and Immunology, Professor of Physical Therapy, and Professor of Occupational Therapy at Washington University. He also is the Director and Principal Investigator of the Charles F. and Joanne Knight Alzheimer’s Disease Research Center. He studies various aspects of Alzheimer disease.
Based on your experience in dementia research in the western world, what would be you suggestions to Indian researchers or researchers focussing on dementia in India?
In the US, the only area where we have done really well in approaching the issue of dementing illness is a combination of clinical research in following patients and healthy control people to see how the disease progresses in them in conjunction with basic science. So the two work together and not separately. In IISc, there is tremendous basic research but no or very little clinical research. In the US, we have exclusive Alzheimer’s research centres that are funded by national institute of health which started in 1984 and since then they have brought clinical and basic science people together. It’s not a tradition in India but I would say that is the only way to advance research in dementia here.
Do you think that lifestyle changes in Indians could help curb the rising number of dementia affected people here?
No one knows the answer yet but it might be possible. That makes India a wonderful place for this kind of research because of the diverse populations, cultures and lifestyles – diet, aging, obesity etc. factors can be checked for their links to dementia. India makes for a perfect laboratory to check for these questions and examine them in clinical cohorts. There will be a lot of challenges to that. Also the population above 65 is much lower in India as opposed to the US or Japan but the existing number is huge and it is only going to get bigger. Hence there is an imperative to do this research.
Available drugs have failed to stop or delay dementia. The ongoing genetic research in that direction is also in its nascent stages. Is there any other alternative that can help deal with dementia in the present situation?
Two paths that we haven’t tried –
- Administering past failed drugs during the earlier course of the disease, right when the symptoms show up. The research has just begun in that aspect.
- Using combination of drugs- each drug attacking a different mechanism leading to dementia. This is yet to start.
A minor fault in any member of the team of proteins carrying structural elements for melanin pigment maturation could deprive us of not just our colour, but could be fatal when combined with few other factors.
Trucks and lorries rule the world of cargo delivery. Any malfunction in them affects the timely delivery of the cargo at the destination and where and how they are used in the further processes. This chain of events is not very different at a cellular level. Our cells also have their own transport pathways responsible for the cargo delivery at the right destination at the right time. Any variations to that system shows up as symptoms to fatal diseases. Dr. Subba Rao and team from the Indian Institute of Science, Bangalore, unravel the nitty gritties of one such transport pathway in animal cells where failure to deliver the cargo, in this case melanin synthesizing enzymes, could result in fatalities.
Melanin pigments are responsible for the colour of our skin and also play an important role in protection against radiations and any other damage from light. Melanin pigment is produced in cellular organelles called melanosomes which need melanin synthesizing enzymes transported from other organelles. The enzymes transported into premature melanosomes facilitate the maturation into fully pigmented melanosomes. The transport pathway is completed with the help of four multi subunit protein complexes, BLOC 1, 2, 3 and Adaptor protein 3 complex.
BLOC 1 consists of 8 subunits, functioning in the upstream of the pathway while BLOC 2, a 3-subunit protein complex, functions towards the end of the pathway in directing the transfer of molecules towards maturing melanosomes for subsequent reactions. It does so by the specific method of “tethering” or by stabilizing the intermediate molecules that need to be transported.
Mutations in BLOC 1 or BLOC 2 proteins result in inefficient delivery of melanin synthesizing proteins to melanosomes and thus failure in full expression of the melanin pigment. This malfunction manifests in the form of albinism of skin, ear and eye, also referred to as oculocutaneous albinism. This is one of the primary symptoms in Hermansky-Pudlak Syndrome (HPS). The other symptoms are lung infections, which are mistaken as Tuberculosis in most cases in India. Both the lung pathology and albinism put together result in HPS but the confirmatory diagnosis is genetic sequencing of the patient and the parents. HPS generally shows up in children within the age group of 4-6. Out of the 16 possible genetic mutations that can result in HPS, only 9 are known so far. Three out of those nine subtypes are a result of mutations to the BLOC 2 protein.
Even though BLOC 1 and 2 play their respective roles in the overall transport pathway, their molecular functions are not yet clear. There are additional proteins that are responsible for membrane trafficking throughout the cell in most transport pathways. These proteins are called Soluble NSF (N-ethylmaleimide sensitive fusion proteins) Attachment Protein REceptor (SNARE). SNARE proteins, a family of about 60 proteins has been known for their role in membrane fusion during transfer of information. For the first time, the team from IISc has identified two members from the SNARE family that are involved in the transport pathway to melanosome. Immortal melanocyte cell lines from mice, both wild type and mutated, were used for the experiments. The expression of these cell lines were estimated by their absorbance at certain wavelengths and compared with levels of protein expressions found in healthy cells. The team concluded that not only do SNAREs play a vital role in the endosome and melanosome membrane trafficking but are also responsible for maintaining the melanosomal proteins in their stable states until delivered to the maturing melanosomes. Very strong interactions between the SNARE proteins and BLOC 1 has been reported in the initial steps of the transport pathway.
Dr. Subba Rao and team intends to further work on uncovering the details of the interactions between the SNAREs and BLOC 1 and 2 complexes. It is important to understand the specific roles that BLOC 2 plays in the cell and would help in filling the gaps in the transport pathway. How and what delivers the cargo at the destination is yet to be understood. Whether the membranes actually fuse for the transport of the proteins or only the proximity of molecules with the opposite membrane to the surface completes the transport? What are the guiding proteins? If the SNAREs go back to their respective states after the transfer is completed? These are few questions the team is looking forward to resolve in their future research.
December 1, 2014
A stitch in time saves nine, goes the old saying. And here a team of scientists at Indian Institute of Science study RAGs (recombination activating genes) to understand the stitching and unstitching of the DNA, which in certain ways leads to genomic instability and cancer.
The RAG complex consists of two genes, RAG1 and RAG2. These genes produce the RAG proteins – RAG1 and RAG2 — which are expressed in the B and T cells of our immune system. The B and T cells help in locating and dealing with foreign substances that enter our bodies like bacteria and other microbes. The cells can recognise foreign bodies using proteins on their surfaces. The RAG gene complex helps in the generation of these surface proteins.
The high number of surface proteins that need to be produced sometimes leads to genomic instability and “chromosomal translocations” – rearrangement of bits of the chromosome, which can lead to incorrect arrangement of genes. This can lead to diseases like lymphoma and leukemia.
In a previous study, Dr. Sathees C Raghavan and Rupa Kumari showed that RAG proteins cleave DNA when they spot a particular sequence of nucleotides. In this paper, they have focussed on studying the factors that can regulate DNA cleavage efficiency of the RAG proteins. This can improve our understanding of how the DNA cleaving activity of these genes is turned on and off.
They found that apart from the sequence of a particular DNA complex, the sequence of the regions surrounding it are important in determining where the RAG proteins bind and where they cleave. The presence of cytosine and thymine in a single stranded region of the DNA complex dictates the position of nicking. A minimum of two cytosines are required for the RAGs cleavage efficiency. The deletion of certain sequences could result in the loss of sequence specific nuclease activity of RAG but it retains its structure specific nuclease activity.
The further understanding of these factors which regulate the stability of the above mentioned DNA complex could help us decipher the mutations that act as the root causes leading to cancers like lymphoma and leukemia.
The paper has been published online on 14th November in The FEBS Journal. http://onlinelibrary.wiley.com/doi/10.1111/febs.13121/abstract
October 20, 2014
Insects like honeybees and ants live in groups that constantly communicate with each other. In fact, communication networks in some insect groups have been successfully compared to artificial technological information transfer networks. Drawing parallels between such highly coordinated processes in living organisms and their artificial counterparts, a team of scientists from IISc, IISER-Kolkatta and BITS-Pilani, seek a better understanding of network communication, to improve the existing information processing networks.
The survival of living organisms depend on the well-coordinated processes at different levels – the cellular and genetic levels, for example. Group living animals take coordination to a different level — schools of fish and flocks of birds rely on competent communication by every individual to all other members, at every point in time. Efficient transfer of information happens through communication systems, which hold good even when there are time or energy constraints.
Among non-human living beings, social insects like bees have some of the most complex societies. Scientists study them to understand communication between the members of a colony, which ensures division of labour between thousands of individuals. Different species of social insects have different modes of communication: bees in large colonies communicate using chemical cues or pheromones, while wasps in smaller colonies use direct physical interactions.
Anjan Nandi and colleagues have studied a tropical wasp Ropalidia marginata to understand the flow of information within a colony. They found that the flow of information between individuals is by pairwise physical interactions, like dominance behaviour, which plays a major role in the regulation of activities of the workers in a colony. For example, foragers that find food receive more dominance over the non foragers, and the extent of dominance varies depending on the circumstances (higher during starvation while lesser during excess food). Apart from dominance, wasps also use paired behaviours like grooming, soliciting and food sharing for flow of information.
There are also global structures that emerge from the two way interactions: the average path length for communication and the average density of interactions could be determined from individual interactions. In other words, the building blocks of a network formation is identified by studying the local structural elements.
The analysis revealed that networks constructed from dominance behaviour in Ropalidia marginata is structurally similar to different biological and technological regulatory networks. Further, the networks are sufficiently robust and capable of efficient information transfer. Even though one would expect a wasp colony to be less complex because it has fewer individuals, a comparison demonstrates that there is a common design principle involved in different biological systems who have evolved to perform similar tasks
The paper was published in the journal Royal Society journal Interface during second week of October 2014.
February 2, 2015
You may worry that intelligent robots will replace humans any day, but that isn’t happening anytime soon. For now, the best computer algorithms cannot do even simple visual tasks like recognizing distorted letters. This is exploited each time we are asked to recognize distorted letters on website. These tests – called CAPTCHAS (for Completely Automated Public Turing test to tell Computers and Humans Apart) – are ubiquitous on the internet because they can prevent access to malicious computer programs. So what makes our brain so good at vision?
Through decades of research, neuroscientists have now found that there’s much more to vision than meets the eye. The eye works much like a camera. Light enters through the pupil and the lens focuses light onto a screen called the “retina”, which is akin to a camera film. Neurons leaving the retina carry information about the image to the visual areas in the brain, which occupy as much as 40% of the total real estate in the brain. This disproportionate area occupied by vision in the brain shows that vision is not easy for the brain either.
Dr SP Arun and his team have been studying biological vision at the Centre for Neuroscience, Indian Institute of Science, Bangalore. In a recent study, Arun and PhD student Ratan Murty have shed light on how the brain interprets the 2-dimensional image falling on the retina. “The image on the retina contains relevant as well as irrelevant information,” Arun says, “The same object can produce different images because of changes in lighting, size, position and three dimensional rotations. These irrelevant variations have to be factored out by the brain for it to understand that all these images belong to the same object. This computation is performed by neurons in the visual cortex.”
Ratan and Arun have performed recordings from the inferior temporal cortex of the monkey brain — an area that is known to be crucial for visual object recognition. They have found that flashing an image results in neural activity that builds up and drops over a period of time. During the build-up of the response, neurons are sensitive to irrelevant variations such as changes in the view point of an object. But in the later portion of the response, neurons respond to the same object ignoring irrelevant stimuli. “This transition from view dependence to view invariance has never been shown before, and it shows that neurons in this area perform this important computation dynamically over time”, said Ratan.
Ratan and Arun are performing a number of other experiments to understand how the brain processes three dimensional information. “Precisely how the brain ignores all the irrelevant variations is a fundamental problem in vision,” Ratan adds, “My experiments will help us understand at least the problem of viewpoint invariance better.” The researchers believe it is something that the brain has learned to solve over the course of evolution. Robots may beat us at algorithmic games like chess but they are nowhere near human competence in real-world tasks like vision.
The paper appeared online in the Journal of Neurophysiology during early 2015. http://jn.physiology.org/content/early/2015/01/16/jn.00810.2014
October 6, 2014
A system to package and deliver drugs to each cell of your body, depending on its needs, has been developed at IISc. “Nanocapsules” made from a special type of material can now deliver drugs right inside cancer affected cells in the body.
“Drug delivery systems” are mechanisms that can be programmed to release drug molecules at targeted cells in the body, using physiological cues present in the body itself. The major hurdle has been that these local cues are not consistent between cells; one needs systems that respond to multiple such cues. Prof. Ashok M Raichur and his team of scientists at the Indian Institute of Science, Bangalore, have demonstrated one of the very few systems that can respond to multiple cues.
There are three ideal characteristics that a drug delivery system should have: (1) the entire drug molecule should be encapsulated, which would prevent its premature release or degradation (2) it should carry the drug safely — and specifically — to the target site and (3) at the target site, it should release the drug molecules using the local physiological cues available.
Hollow nanocapsules were fabricated from special materials called biopolymers, which are materials that do not react with body tissues. These nanocapsules contain components that can respond to local cues integrated in the walls. To avoid premature release of the drug, the walls are crosslinked; this sort of architecture gives scope to load large amounts of drugs into the capsule. The wall structure also makes it possible for a small amount of local cues, like enzymes, to trigger the release of a large number of drug molecules.
The Food and Drug Administration(FDA) approved drug, polypeptide protamine (PRM), used to treat heparin induced toxicity, is one of the stimuli responsive components which is identified and actively cleaved into smaller fragments by trypsin like enzymes. The second component, chondroitin sulphate is susceptible to cleavage by enzyme hyaluronidase and has been used in the treatment of arthritis.
The Layer by Layer (LbL) assembly method used for fabrication of nanocapsules is carried under highly controlled mild conditions and thereby capable of incorporating the sensitive components (biopolymers) used here. It has the capacity to take up an array of materials ranging from small proteins to inorganic molecules. The nanocapsule surface was combined with a molecule used to identify cancer cells, folic acid (Vitamin B9, as we know it).
The drug delivery system was demonstrated using a population of cells in the lab – something called a “cell line”.
The paper appeared in the international journal RSC Advances on 17th September. http://pubs.rsc.org/en/content/articlelanding/2014/ra/c4ra07815b#!divAbs…
September 22, 2014
A protein found in high levels in some cancer cells can be used for treating diseases caused by oxygen free radicals in the body, a recent study has found.
Oxygen free radicals such as hydrogen peroxides and superoxides, called Reactive Oxygen Species (ROS), are found in the cells as byproducts of cellular metabolism. Uncontrolled levels of ROS in the cell can lead to oxidative stress. Diabetes, atherosclerosis and neurodegenerative diseases like Parkinson’s and Alzheimer’s disease find their roots at the damage caused by oxidative stress in the cells.
Patrick D’Silva’s group at the Indian Institute of Science have found that Magmas, a mitochondrial protein also regulates the level of ROS in cells, apart from its already known function.
Magmas is involved in protein transport in cells, and is found in elevated levels in certain cancer types. There is very little information already available about regulation of ROS in the body, and this paper brings forth a lot of missing links in this research area.
The team found that the levels of Magmas in the cell are dependent on the cellular ROS levels. Elevated levels of Magmas help in lowering the concentration of ROS and vice versa. It not only plays an important role in controlling the production of free radicals, but maintains the ROS homeostasis by efficient scavenging. This protects the cell viability and also increases cellular stress tolerance.
“By maintaining a free-radical balance in cell, this protein prevents stress mediated cellular damage to biomolecules such as DNA, proteins and lipids. Hence, overproduction of Magmas protein provides unique advantages to the cells against free radical stress”, said Prof D’Silva.
Higher levels of Magmas are typically found in metabolically active tissues, cancer cells and tissues at different developmental stages. In cancer cells, Magmas prevents cell death, and hence helps in the proliferation of cancer cells. Even in non-cancerous cells, Magmas shows controlled levels of ROS and much lesser oxidative stress.
Such molecules that regulate the number of free radicals can be used while designing possible therapies for oxidative stress related disorders. “The inhibitors or stimulators against Magmas can be used as a therapeutic intervention against cancer as well as multiple free-radical induced stress related diseases”, said Prof D’Silva.
Further research is required to elucidate the mechanism of ROS regulation by Magmas and to discover the other proteins involved in the regulatory circuit.
The paper appeared in the journal Cell Death and Disease on 28th August 2014.