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Nobel and other Prizes
Cells’ Toolbox for DNA repair honoured with Nobel Prize in Chemistry
The Nobel Prize in Chemistry 2015 is awarded to Tomas Lindahl (UK), Paul Modrich (USA) and Aziz Sancar (USA) for having mapped, at a molecular level, how cells repair damaged DNA and safeguard the genetic information.
Their work has provided fundamental knowledge of how a living cell functions and is, for instance, used for the development of new cancer treatments.
What’s the DNA repair toolbox ?
Each day our DNA is damaged by UV radiation, free radicals and other carcinogenic substances, but even without such external attacks, a DNA molecule is inherently unstable.
Thousands of spontaneous changes to a cell’s genome occur on a daily basis. Furthermore, defects can also arise when DNA is copied during cell division, a process that occurs several million times every day in the human body.
The reason our genetic material does not disintegrate into complete chemical chaos is that a host of molecular systems continuously monitor and repair DNA.
The Nobel laureate scientists, who have mapped how several of repair systems function at a detailed molecular level.
Tomas Lindahl – Puts together the pieces of base excision repair
In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.
This was the start of 35 years of successful work, during which Tomas Lindahl has found and examined many of the proteins in the cell’s toolbox for DNA repair.
Bit by bit, Lindahl pieced together a molecular image of how base excision repair functions, a process in which glycosylases, enzymes similar to the one he had found in 1974, are the first step in the DNA repair process.
Base excision repair also occurs in human beings and, in 1996, Tomas Lindahl managed to recreate the human repair process in vitro.
The decisive factor for Tomas Lindahl was the realisation that DNA inevitably undergoes change, even when the molecule is located in the cell’s protective environment. However, it had long been known that DNA can be damaged by environmental assaults such as UV radiation.
The mechanism used by the majority of cells to repair UV damage, nucleotide excision repair, was mapped by Aziz Sancar, born in Savur, Turkey, and professionally active in the USA.
Aziz Sancar’s Nucleotide excision repair
Aziz Sancar has mapped nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances, among other things.
Aziz Sancar’s ability to generate knowledge about the molecular details of the process changed the entire research field. He published his findings in 1983.
He mapped the next stages of nucleotide excision repair. In parallel with other researchers, including Tomas Lindahl, Sancar investigated nucleotide excision repair in humans.
The molecular machinery that excises UV damage from human DNA is more complex than its bacterial counterpart but, in chemical terms, nucleotide excision repair functions similarly in all organisms.
Paul Modrich – illustrating DNA mismatch repair
Once his father, a biology teacher, said: “You should learn about this DNA stuff.” This was in 1963, the year after James Watson and Francis Crick had been awarded the Nobel Prize for discovering the structure of DNA.
A few years later, that “DNA stuff” really became central to Paul Modrich’s life.
Paul Modrich has demonstrated how the cell corrects errors that occur when DNA is replicated during cell division. This mechanism, mismatch repair, reduces the error frequency during DNA replication by about a thousandfold. Congenital defects in mismatch repair are known, for example, to cause a hereditary variant of colon cancer.
In conclusion, the basic research carried out by the 2015 Nobel Laureates in Chemistry has not only deepened our knowledge of how we function, but could also lead to the development of lifesaving treatments.
In the words of Paul Modrich: “That is why curiosity-based research is so important. You never know where it is going to lead… A little luck helps, too.”
Irish-born William Campbell and Japan’s Satoshi Omura won half of the prize for discovering avermectin, a derivative of which has been used to treat hundreds of millions of people with river blindness and lymphatic filariasis, or elephantiasis.
China’s Tu Youyou was awarded the other half of the prize for discovering artemisinin, a drug that has slashed malaria deaths and has become the mainstay of fighting the mosquito-borne disease. She is China’s first Nobel laureate in medicine.
Lets’s talk about Satoshi Omura’s invention
So, how did the journey start for Satoshi Omura?
Satoshi Omura, a Japanese microbiologist and expert in isolating natural products, focused on a group of bacteria, Streptomyces, which lives in the soil and was known to produce a plethora of agents with antibacterial activities (including Streptomycin discovered by Selman Waksman, Nobel Prize 1952).
Equipped with extraordinary skills in developing unique methods for large-scale culturing and characterization of these bacteria, Omura isolated new strains of Streptomyces from soil samples and successfully cultured them in the laboratory.
From many thousand different cultures, he selected about 50 of the most promising, one of these cultures later turned out to be Streptomyces avermitilis, the source of Avermectin, a medicine that has nearly eradicated river blindness and radically reduced the incidence of filariasis, which can cause the disfiguring swelling of the lymph system in the legs and lower body known as elephantiasis.
Puzzle about River Blindness?
Also known as onchocerciasis or Robles’ Disease, is caused by transmission of the parasitic worm Onchocerca volvulus by black flies of the genus Simulium. Vector lives near rivers, thus the name.Inside the host, the worms create larvae that travel to the skin, and infect other flies that bite the victim.
Symptoms include severe itching, eruptions under the skin, and blindness. About 17-25 million are infected; some 0.8 million have some degree of vision loss. Most infections in sub-Saharan Africa.
Then, what about Lymphatic Filariasis or Commonly known as elephantiasis ?
It is tropical disease caused by transmission of parasites classified as nematodes (roundworms) of the family Filariodideato, to humans by mosquitoes.
Adult worms lodge in lymphatic system and disrupt immune system. Causes abnormal enlargement of body parts, pain, severe disability and social stigma.
Over 120 million people are infected, about 40 million disfigured or incapacitated. About 1.23 billion in 58 countries are threatened, 80% of whom live in 10 countries, including India, Bangladesh and Nepal.
Our next Pioneer William C. Campbell
An expert in parasite biology working in the USA, acquired Omura’s Streptomyces cultures and explored their efficacy.
Campbell showed that a component from one of the cultures was remarkably efficient against parasites in domestic and farm animals.
The bioactive agent was purified and named Avermectin, which was subsequently chemically modified to a more effective compound called Ivermectin.
Ivermectin was later tested in humans with parasitic infections and effectively killed parasite larvae (microfilaria) .
Collectively, Omura and Campbell’s contributions led to the discovery of a new class of drugs with extraordinary efficacy against parasitic diseases.
What a breakthrough, China’s first Nobel laureate in medicine, Let’s talk about it?
Ms. Youyou Tu, won Nobel in Medicine for a therapy against malaria.
Malaria was traditionally treated by chloroquine or quinine, but with declining success. By the late 1960s, efforts to eradicate Malaria had failed and the disease was on the rise.
At that time, Youyou Tu in China turned to traditional herbal medicine to tackle the challenge of developing novel Malaria therapies.
Tu revisited the ancient literature and discovered clues that guided her in her quest to successfully extract the active component from Artemisia annua.
Tu was the first to show that this component, later called Artemisinin, was highly effective against the Malaria parasite, both in infected animals and in humans.
Artemisinin represents a new class of antimalarial agents that rapidly kill the Malaria parasites at an early stage of their development, which explains its unprecedented potency in the treatment of severe Malaria.
How do you think these inventions will change the world?
The discoveries of Avermectin and Artemisinin have fundamentally changed the treatment of parasitic diseases.
Ivermectin is highly effective against a range of parasites, has limited side effects and is freely available across the globe.
The importance of Ivermectin for improving the health and wellbeing of millions of individuals with River Blindness and Lymphatic Filariasis, primarily in the poorest regions of the world, is immeasurable.
Treatment is so successful that these diseases are on the verge of eradication, which would be a major feat in the medical history of humankind. Malaria infects close to 200 million individuals yearly.
Artemisinin is used in all Malaria-ridden parts of the world. When used in combination therapy, it is estimated to reduce mortality from Malaria by more than 20% overall and by more than 30% in children. For Africa alone, this means that more than 100 000 lives are saved each year.
The discoveries of Avermectin and Artemisinin have revolutionized therapy for patients suffering from devastating parasitic diseases.
Campbell, Ōmura and Tu have transformed the treatment of parasitic diseases. The global impact of their discoveries and the resulting benefit to mankind are immeasurable.
Published with inputs from Arun
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Gravitational Wave Observations
Eureka moment: Gravitational waves found
Recently, Gravitational waves, the cosmic ripples that distort space-time itself, have been directly detected for the first time. Let’s know about this unprecedented discovery!
What is so special about this eureka moment?
- For the first time, scientists have observed ripples in the fabric of space-time called gravitational waves, arriving at the earth from a cataclysmic event in the distant universe
- This confirms a major prediction of Albert Einstein’s 1915 general theory of relativity and opens an unprecedented new window onto the cosmos
- Physicists have concluded that the detected gravitational waves were produced during the final fraction of a second of the merger of two black holes to produce a single, more massive spinning black hole
- This collision of two black holes had been predicted but never observed
Let’s first know about Albert Einstein’s general theory of relativity?
- In 1905, Albert Einstein determined that the laws of physics are the same for all non-accelerating observers, and that the speed of light in a vacuum was independent of the motion of all observers. This was the theory of special relativity
- It introduced a new framework for all of physics and proposed new concepts of space and time
- Einstein then spent 10 years trying to include acceleration in the theory and published his theory of general relativity in 1915
- In it, he determined that massive objects cause a distortion in space-time, which is felt as gravity
[ Einstein’s mathematics showed that massive accelerating objects (such as neutron stars or black holes orbiting each other) would disrupt space-time in such a way that ‘waves’ of distorted space would radiate from the source ]
What are Gravitational waves?
Cataclysmic events, such as this artist’s rendition of a binary-star merger, are believed to create gravitational waves that cause ripples in space-time. Credits: NASA
- Gravitational waves are distortions or ‘ripples’ in the fabric of space-time caused by some of the most violent and energetic processes in the Universe
- These ripples would travel at the speed of light through the Universe, carrying with them information about their cataclysmic origins, as well as invaluable clues to the nature of gravity itself
What are the Sources of Gravitational Waves?
- Any object with mass that accelerates (which in science means changes position at a variable rate, and includes spinning and orbiting objects) produces gravitational waves, including humans and cars and airplanes etc.
- But the gravitational waves made by us here on Earth are much too small to detect
- The strongest gravitational waves are produced by catastrophic events such as colliding black holes, the collapse of stellar cores (supernovae), coalescing neutron stars or white dwarf stars, the slightly wobbly rotation of neutron stars that are not perfect spheres, and the remnants of gravitational radiation created by the birth of the Universe itself
Not one but four types of Gravitational Waves!
- In order to understand the types of gravitational waves, Laser Interferometer Gravitational Wave Observatory (LIGO) scientists have defined 4 categories of gravitational waves
- These categories are: Continuous Gravitational Waves, Compact Binary Inspiral Gravitational Waves, Stochastic Gravitational Waves, and Burst Gravitational Waves
But, Why Detect Them?
- This will open up a new window of study on the Universe, giving us a deeper understanding of these cataclysmic events, and usher in brand new cutting-edge studies in physics, astronomy, and astrophysics
- More importantly, since gravitational waves don’t interact with matter (unlike electromagnetic radiation), they travel through the Universe completely unimpeded giving us a crystal clear view of the gravitational wave
- This will provide astronomers and other scientists, first glimpses of previously unseen and unseeable wonders, and greatly adding to our understanding of the nature of space and time itself
So, How does LIGO come into the Picture?
- LIGO( Laser Interferometer Gravitational Wave Observatory) is the world’s largest gravitational wave observatory and a cutting edge physics experiment
- LIGO exploits the physical properties of light and of space itself to detect and understand the origins of gravitational waves
- LIGO has 2 widely separated identical detector sites working in unison as a single “observatory”: one in Hanford, southeastern Washington State and the other in rural Livingston, Louisiana
- LIGO has a very close collaboration with the VIRGO collaboration that analyzes data from VIRGO, a 3 km gravitational wave interferometer located near Pisa, Italy
- Data from LIGO and Virgo are combined and analyzed together by the LIGO and Virgo collaborations
- Thus significantly increasing the capability of combined data for detecting and using gravitational waves to learn about nature
Is there any Way ahead for India?
Image – Locations of existing gravitational-wave detectors, and how far out a LIGO in India would be. Source: LIGO
- Yes, because Union cabinet has approved a proposal to establish a state-of-the-art gravitational wave observatory in India in collaboration with LIGO in the US
- The project will bring unprecedented opportunities for scientists and engineers to dig deeper into the realm of gravitational wave and take global leadership in this new astronomical frontier
- This will also bring considerable opportunities in cutting-edge technology for the Indian industry which will be engaged in the construction of the 8-km long beam tube at ultra-high vacuum on a leveled terrain
- With its establishment, India will join the global network of gravitational wave detectors
- The establishment of an observatory in India assumes importance because the further the distance between the observatories, the greater will be the accuracy in locating gravity waves
- Maharashtra and Madhya Pradesh are among the states shortlisted for the experiment
Can we expect some answers from you guys?
#Q. Recently, Union cabinet has approved a proposal to establish a gravitational wave observatory, one of the mega science projects in India. Discuss, how will this project help India if it becomes a reality.
Published with inputs from Arun | Image: space.com
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Genetically Modified (GM) crops – cotton, mustards, etc.
Genetically Modified Organisms(GMO): Developments and Concerns
Recently, Genetic Engineering Appraisal Committee (GEAC) decided to put on hold the government’s decision to commercialise genetically modified (GM) mustard, because of growing outrage by farmer groups against it. Let’s understand its basics in brief!
What is GMO?
- GMOs can be defined as organisms (i.e. plants, animals or microorganisms) in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating and/or natural recombination
- It allows selected individual genes to be transferred from one organism into another, also between non related species
- Foods produced from or using GM organisms are often referred to as GM foods
- Recently in India, GM mustard crop was introduced, which was later withdrawn. There is a raging debate going on advantages and disadvantages of GMOs
- For a long time, further study was requested by farmers, environmentalist on GMO crops
<Genetic Engineering Appraisal Committee (GEAC) is a body under the Environment Ministry that regulates the use of genetically modified organisms>
Why are GM foods produced?
- GM foods are developed – and marketed – because there is some perceived advantage either to the producer or consumer of these foods
- This is meant to translate into a product with a lower price, greater benefit (in terms of durability or nutritional value) or both
- Initially GM seed developers wanted their products to be accepted by producers and have concentrated on innovations that bring direct benefit to farmers (and food industry generally)
- One of the objectives for developing plants based on GM organisms is to improve crop protection
What really is India’s recently developed GM mustard?
- A team of scientists at Delhi University led by former vice-chancellor Deepak Pental has bred DMH-11, a genetically modified (GM) mustard hybrid
- Hybrids are normally obtained by crossing two genetically diverse plants from the same species
- The first-generation offspring resulting from it has higher yields than what either of the parents is individually capable of giving
- But there is no natural hybridisation system in mustard, unlike in, say, cotton, maize or tomato
- What team has done is, that they have created a viable hybridisation system in mustard using GM technology
- The resulting GM mustard hybrid, it is claimed, gives 25-30% more yield than the best varieties such as ‘Varuna’ currently grown in the country
Is there a need, in the first place, for developing a mustard hybrid?
- In 2014-15, India imported 14.5 million tonnes of edible oils valued at $10.5 billion
- With the country’s own annual edible oil production stuck at below 7.5 million tonnes, of which mustard’s share is roughly a quarter
- So, there is need to raise domestic crop yields and cut dependence on imports
- Hybrid technology is a potential technique to boost yields, as has been successfully demonstrated in a host of crops
What are the environmental risks?
- GMOs contaminate forever. GMOs cross pollinate and their seeds can travel far and wide
- It is impossible to fully clean up our contaminated gene pool
- Genetic engineering allows plants to survive high doses of weed killers, resulting in higher herbicide residues in our food
- GMO crops are creating ‘super weeds’ and ‘super bugs,’ which can only be killed with more toxic poisons
Are there any advantages?
Insect Resistance
- Some GMO foods have been modified to make them more resistant to insects and other pests
- This means the amount of pesticide chemicals used on the plants are reduced, so their exposure to dangerous pesticides are also reduced
Stronger Crops
- Another benefit that GM technology is believed to bring about is that crops can be engineered to withstand weather extremes and fluctuations,
- This means that there will be good quality and sufficient yields even under a poor or severe weather condition
Environment Protection
GM crops often requires less time, tools and chemicals, and may help with reducing greenhouse gas emissions, soil erosion and environmental pollution
More Nutritious Foods
According to the UN Food and Agricultural Organization (FAO), some GM foods have been engineered to become more nutritious in terms of vitamin or mineral content.
Economic Benefits
- Larger production leading to increased farm income, reduced poverty, low food prices and thus reduced hunger and malnutrition.
- Besides new food products are also included, diversifying food varieties
Then, Why has there been so much concern about GM foods among some public interest groups, activists and consumers?
- Since the first introduction on the market in the mid-1990s of a major GM food (herbicide-resistant soybeans), there has been concern about such food among activists and consumers, especially in Europe
- In fact, public attention has focused on the risk side of the risk-benefit equation, often without distinguishing between potential environmental impacts and public health effects of GMOs
- Consumers have questioned the validity of risk assessments, both with regard to consumer health and environmental risks, focusing particulary on long-term effects
- Consumer concerns have triggered a discussion on the desirability of labeling GM foods, allowing for an informed choice of consumers
What further developments can be expected in the area of GMOs?
- GM organisms are likely to include plants with improved resistance against plant disease or drought, crops with increased nutrient levels, fish species with enhanced growth characteristics
- For non-food use, they may include plants or animals producing pharmaceutically important proteins such as new vaccines
Published with inputs from Arun
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Zika Virus Outbreak
Everything you wanted to know about Zika virus
The World Health Organization (WHO) expects that Zika virus, a mosquito-borne disease, spreading through the Americas, to affect between 3 million and 4 million people. Let’s analyse this in brief!
Where was the first Zika virus outbreak identified?
- Zika virus is an emerging mosquito-borne virus that was first identified in Uganda in 1947 in rhesus monkeys through a monitoring network of sylvatic yellow fever.
- It was subsequently identified in humans in 1952 in Uganda and the United Republic of Tanzania.
- Outbreaks of Zika virus disease have been recorded in Africa, the Americas, Asia and the Pacific.
Trivia : Do you know why is it called Zika Virus?
It was first isolated from Rhesus monkeys in Zika forest near Lake Victoria in Uganda.
Find Out why was Ebola virus named as such?
What makes this outbreak different?
- The current outbreak, the first ever in the western hemisphere, is a big deal for a number of reasons
- We now know that it’s not adults who have the most to lose but their unborn babies
- Microcephaly is a condition where a baby is born with an abnormally small head and brain defects
- Worldwide it affects only 1 in 30,000 to one in 250,000 newborns
- In Brazil there are usually a few hundred cases annually at most, but since October 2015, there have been 3,500 new microcephaly cases
But, what is microcephaly?
- Microcephaly is a rare condition where a baby has an abnormally small head.
- This is due to abnormal brain development of the baby in the womb or during infancy.
- Babies and children with microcephaly often have challenges with their brain development as they grow older.
- Microcephaly can be caused by a variety of environmental and genetic factors such as Downs syndrome; exposure to drugs, alcohol or other toxins in the womb; and rubella infection during pregnancy.
How does the Zika virus spread?
- Zika virus is transmitted to people through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions
- This is the same mosquito that transmits dengue, chikungunya and yellow fever
- Zika virus disease outbreaks were reported for the first time from the Pacific in 2007 and 2013 (Yap and French Polynesia, respectively), and in 2015 from the Americas (Brazil and Colombia) and Africa (Cape Verde)
How bad is it now?
- As of January 23, 2016, the Zika virus has spread to 21 countries and territories of the Americas
- It’s speculated that the virus must have arrived in Brazil along with the throngs that swept in during the 2014 FIFA World Cup
- Things look so grim that governments of 4 South American countries are now advising women to not get pregnant until the situation is brought under control
- The WHO has predicted that the virus is likely to spread all over North and South America, except for Chile and Canada where the Aedes aegypti mosquito is not present
- The reason that the WHO thinks these countries are so susceptible is that their populations have not been exposed to the virus before and hence have no immunity
Is there a cure?
- No, there isn’t. There exists medication for symptomatic relief but these are quite useless now that we know about the microcephaly link
- Research on the Zika virus is still quite primitive
- Given its generic symptoms in adults, it’s very easy to miss or misdiagnose
- Moreover, the virus doesn’t seem to show effects in common lab animals like mice and rats. Getting monkeys is extremely tough because of restrictions on primate research
- Vaccine development and antiviral drug discovery efforts are on but this takes time, and with the Zika virus, we’ll be starting from scratch
Does Brazil have a way out?
- Brazil needs an immediate plan of action for more than one reason
- Rio de Janeiro is frantically spraying insecticides at the parade grounds where the annual carnival celebrations will commence soon
- In August, the city is due to host the Olympics
What about India?
- India is one of the Aedes aegyptis’s many homes but the Zika virus itself has not ever been detected in our country so far
- However, in a study in the 1950s, healthy individuals from 6 Indian states showed passive immunity to the virus
- This means that though their blood contained antibodies against the virus, this was not because they were exposed to the virus
- Usually passive immunity is acquired through vaccines, from mother-to-child transmissions or breast milk
- In the case of India, where the Zika virus is not known to exist, the antibodies probably arose from exposure to similar viruses
- Nevertheless, theoretically, Zika can spread anywhere that the mosquito exists
- That means India, too. Indians are just as susceptible if they travel to high-risk countries
Is there something more that you wanted to know which we did not answer yet? Drop in with your questions.
Published with inputs from Arun | Image - Outbreaknews