Friday, December 27, 2019

IIT Hyderabad researchers unravel functioning of DNA repair proteins

Researchers are seeking to understand the workings of the DNA damage repair proteins. Certain types of chemicals produced naturally in the body can cause damages in DNA and if not fixed fast, may trigger cell death.

Researchers have unraveled the working of a protein that repairs damaged DNA.


Nature has evolved techniques to not only protect DNA, but also to repair damaged DNA so that catastrophic damage can be averted. In humans, one such repair mechanism involves activation of a special class of proteins called 'DNA' repair proteins.


With increasing awareness of the impact of DNA damage on almost all diseases and maladies, there is a worldwide effort to understand how these repair proteins work, both as an academic exercise and as the foundation for therapeutic interventions.


The results of the study has been published recently.


What makes matter a living being, be it a bacterium or man is the DNA. DNA is the file blueprint of the life-form and encodes the directions that the life-form must take in order to become bacterium, rose, lion or man. It is this essential for the survival of every cell and is usually kept well protected within the nucleus of cells and in some non0nuclear parts like the mitochondria.


Any damage to DNA can result in outcomes that can range from unperceivable mild changes, such as the sudden appearance of a harmless mole, to catastrophic diseases, such as cancer. The retention of DNA integrity is therefore essential for proper function and survival of all organisms. Protection of DNA is daunting because of the possibility of damage by external sources and the intrinsic instability of DNA itself.


" Our laboratory at IIT Hyderabad seeks to understand the working of the DNA damage repair proteins. Certain types of chemicals produced naturally in the body can cause damages in DNA and if not fixed fast, may trigger cell death", explains Dr. Anindya Roy.


Researchers discovered mechanism by which these DNA repair proteins assemble when DNA is under threat. They studies the action of one specific protein called alkB homolog 3 or ALKBH3. It has been known that ALKBH3 repairs alkylated DNA containing 1-methyladenosine and 3.methylcytosine through oxidative demethylation, but the mechanism has hitherto remained unclear.


The researchers unraveled the mechanism by which ALKBH3 brings about demethylation.


We've found that ALKBH3 has a direct protein-protein interaction with another protein called RAD51C and this interaction stimulates ALKHB3-mediated repair of methyl-adduct located within 3'-tailed DNA adds the Dr. on the technical aspects of their discovery.


The team is fascinated by the universality of the mechanism-- it is just as applicable to the bacterium as it is to the humans. " The knowledge gained from our studies might, in the long term, be beneficial from a cancer therapeutic perspective", hopes Dr. Roy, as the team proceeds with work on understanding how DNA repair works.


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Thursday, April 18, 2019

Scientists revive brain funciton in dead pigs

Scientists have managed to restore cell function in the brains of pigs hours after they died, in a breakthrough that experts said threw into question the very notion of what makes animals of even humans--alive.

Authors said their research could one day be used to help treat victims of heart attacks and strokes and unravel the mysteries of brain trauma.


In human and large mammal brains, cells crucial for neural function begin to degrade as soon as blood supply is cut- a process long considered to be irreversible.


But the findings of the trial, show that the brains of pigs can have their blood flow and cell function restored even hours after death.


The team used the brains of 32 pigs that had been slaughtered for food and discarded, without blood or glucose flow for 4 hours each.


Then, using a tissue support system that pumps a liquid designed to mimic blood through organs, they rehydrated the brains for a further 6 hours.


Some brains received the patented life-support solution and others were given a control substance.
The results were astonishing: the brains that recived the artificial blood had basic cell function restored. Their blood vessel structure was revived, and the team even observed some localised processes- including in synapses and immune responses- flickering back to life.


Those that received the control solution turned within hours to what researchers described as something a bit like yoghurt.


I was tremendously surprised, a sresearcher and lead study author said.


We were surprised how well the structure was preserved. We found that cell death is reduced, which is very exciting and promising.


The main conceptual finding is this: cell death in the brain occurs across a longer time period than we previously thought , added the author.


The team stressed that they saw no higher level functional activity, such as electric signalling associated with consciousness in the revived brains.


That is a clinical sign that the brain is alive, and we never found it, he said. This is not a living brain, it is a cellularly active brain.


Had any such activity been detected, the team said they would have had to deliver anaesthetic to the brains to null any pain- despite then having been dead for hours.


If some activity shows up that indicated consciousness, we would have to stop the experiment, said a researcher.


This would be unique: inducing consciousness in an organ that's not connected to any living being.
The findings suggest that scientists may have under appreciated the brain's capacity for self-restoration after a patient is declared brain dead.


But for experts invited to comment on the study, it raised deeper philosophical and ethical questions.
Writing in a linked editorial, a Prof. of law and philosophy said that the study throws into question long-standing assumptions over what makes an animal or a human alive.


She said researchers had inadvertently created an ethical grey area where the pigs used were not alive, but not completely dead.


A Prof. of medical ethics said that the study could have vital implications for future brain research.
This research reminds us that death is less an event, and more of a process that occurs over time, he said.


Cells within the human organism may be alive for some period of time after the person has died.


A researcher said the team planned to use their support system on dead brains for longer periods of time in order to see how the cells react.


We could potentially get some insight into how these brains could be saved, he said.


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