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Friday, 18 March 2016

When Parkinson proteins become toxic to brain cells

Researchers from the University of Cambridge used a non-invasive method to observe the process of Perkinson’s disease that take place in nano-scale to identify potentially the process at which proteins in the brain become toxic, thus leading to death of brain cells. The identified results bring about the story of the same protein that either cause or protect against the toxic effects that lead to death of brain cells. The work reveals the answer of why people develop Parkinson’s and aid in search of potential treatments. The research was published recently in the journal Proceedings of the National Academy of Sciences.

Observation of the point at which proteins associated with Parkinson’s disease become toxic to brain cells could help identify how and why people develop the disease, and aid in the search for potential treatments. (Courtesy: University of Cambridge)
Parkinson’s disease is the second most common neurodegenerative disorder just after well known Alzheimer’s disease. Symptoms like muscle tremors, stiffness, difficulty in walking and finally dementia in later stage.

A super-resolution microscopy techniques was used to look into live neurons without a sheer damage to the tissue. They observed the behaviour of different types of alpha-synuclein, a protein closely associated with Parkinson’s disease. When they added the same protein fibrils to the neurons they acted on the alpha-synuclein present already in the neurons that initiated toxic effects leading to cell death. The damage appeared to be done before visible fibrils are even formed. The researchers then added soluble form of alpha-synuclein together with amyloid fibrils and this can able to turn down the toxic effect of the former. They suggest that amyloid fibrils acted like magnets for soluble proteins to mop up the soluble protein pool shielding the toxic effects.

In conclusion, the findings provide essential information about the damage of the neuron that may happen when there is simply extra soluble protein in the cell; the excess amount of it known to cause toxic effect leading to death of brain cells. Naturally the extra soluble protein may be caused by genetic factors or aging.

Further Reading: University of Cambridge

Journal Source: Dorothea Pinotsi et. al. ‘Nanoscopic insights into seeding mechanisms and toxicity of α-synuclein species in neurons.’ Proceedings of the National Academy of Sciences (2016). DOI: 10.1073/pnas.1516546113

Thursday, 17 March 2016

Scientists for the first time use CRISPR-Cas9 to target RNA in live cells

CRISPR-Cas9 which gained much popularity in editing system of DNA, researchers have applied the same technique for the first time on RNA. University of California, San Diego researchers published the result on March 17, 2016 in the journal Cell.

This is a cell carrying an RNA-targeted Cas9 system that reveals beta-actin mRNA distribution in the cytoplasm. (Courtesy: UC San Diego Health)

The genetic code stored in DNA determines all the bodily mechanisms from colour to susceptibility towards any disease. But this is always not the case which determines the diseases linked to, but does some of them which are linked to RNA. It is the intermediary genetic material that carries the genetic code to knit amino acids to form protein.

Figuring out the location of RNA to be targeted is primarily important for the researchers to go forward. Identifying the location would determine whether proteins are produced at perfect location in appropriate time. This is when scientists brought forward to use CRISPR-Cas9 system, a naturally occurring editing tool for DNA in Bacteria.

CRISPR-Cas9 normally works with a designed RNA targeted against the sequence of DNA to be edited, and the Cas9 enzyme able to degrade the target after proper complementary binding of RNA. The final repair can easily be recovered by the host itself. This whole system until now was limited to DNA, but Yeo and his colleagues at University of California, Berkeley used the same for targeting RNA in live cells, called RNA-targeted Cas9 (RCas9). In order to modify the target from DNA to RNA, they have changed several features in CRISPR-Cas9 system. An associated short designed nucleic acid sequence called PAMmer, along with guide RNA can guide Cas9 to RNA molecule.

Journal Source: David A. Nelles, Mark Y. Fang, Mitchell R. O’Connell, Jia L. Xu, Sebastian J. Markmiller, Jennifer A. Doudna, Gene W. Yeo. Programmable RNA Tracking in Live Cells with CRISPR/Cas9. Cell, 2016; DOI: 10.1016/j.cell.2016.02.054

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