CRISPRCas9

CRISPRCas9

CRISPR-Cas9 is a method of genome editing that exploits a natural DNA-snipping enzyme in bacteria, called Cas9 (CRISPR-associated protein 9) to target and edit particular genes. CRISPR stands for Clustered regularly interspaced short palindromic repeats, which are segments of DNA of a particular structure found widely in bacteria and archaea (prokaryotes). In the wild, the CRISPR-Cas9 system is part of the prokaryotic immune system, which can snip out of the genome DNA acquired from foreign sources such as phages (bacterial viruses). The same molecular machinery is now being used to enable genetic material to be cut from and pasted into the genomes of other organisms, including eukaryotes such as humans. It might offer a tool for curing genetically based diseases.

DNA has become a versatile polymeric substrate for making nanotechnological structures and artificial molecular-scale machinery for computation, pattern formation, and nanoscale assembly. For several decades now, these efforts have drawn on methods developed in and for biotechnology, and similarly they are likely to find ways of exploiting the advantages of the new technique called CRISPR/Cas9 for manipulating DNA. #CRISPRCas9

CRISPR-Cas9 is a method of genome editing that exploits a natural DNA-snipping enzyme in bacteria, called Cas9 (CRISPR-associated protein 9) to target and edit particular genes. CRISPR stands for Clustered regularly interspaced short palindromic repeats, which are segments of DNA of a particular structure found widely in bacteria and archaea (prokaryotes). In the wild, the CRISPR-Cas9 system is part of the prokaryotic immune system, which can snip out of the genome DNA acquired from foreign sources such as phages (bacterial viruses). The same molecular machinery is now being used to enable genetic material to be cut from and pasted into the genomes of other organisms, including eukaryotes such as humans. It might offer a tool for curing genetically based diseases.

DNA has become a versatile polymeric substrate for making nanotechnological structures and artificial molecular-scale machinery for computation, pattern formation, and nanoscale assembly. For several decades now, these efforts have drawn on methods developed in and for biotechnology, and similarly they are likely to find ways of exploiting the advantages of the new technique called CRISPR/Cas9 for manipulating DNA.

FASTER WAY TO PRODUCE SPECIFIC HUMAN ANTIBODIES USING NANOPARTICLES

Treating patient derived B cells with nanoparticles coated with CpG oligonucleotides to stimulate plasma cell production and challenge antigens to designate what kind of antibody the B cells should produce has resulted in the generation of specific, high affinity antibodies in just a few days that can recognize several strains of a pathogen at the same time. The researchers have already produced antibodies to a variety of bacterial and viral antigens, including tetanus toxoid and several strains of influenza, and were able to generate anti HIV antibodies from B cells donated by healthy volunteers who did not have the disease.

The new technique also eliminates the need for previous exposure to the pathogens, either by vaccination or infection.

"Our technique should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals," said Dr. Facundo Batista, who led the team from the Francis Crick Institute in London, the Ragon Institute of Massachusetts General Hospital, MIT and Harvard. "In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens."

Antibodies are produced by white blood cells called B cells, which recognize the calling card of a bacteria or virus called an antigen, and transform into plasma cells tailored to produce large numbers of antibodies to that specific antigen that fight off the disease. That's what happens in the body. When scientists tried to reproduce the process in the lab, they ran into problems getting the B cells to make the specific kind of plasma cells they needed because the challenge antigens were missing.

It was easy to get the B cells to proliferate by adding short DNA fragments called CpG oligonucleotides into their culture medium. CpG oligonucleotides activate a protein inside B cells TLR9, but TLR9 enthusiastically stimulates every B cell in the sample to respond, not just the tiny fraction capable of producing a particular antibody. Batista and his colleagues attached both CpG oligonucleotides and real challenge antigens to nanoparticles, added them to B cell cultures, and the plasma cells that resulted were both abundant and pathogen specific.

The team hopes their approach will help researchers produce therapeutic antibodies to treat infectious disease and other conditions, such as cancer.

For more information, go to the Journal of Experimental Medicine
http://jem.rupress.org/cgi/doi/10.1084/jem.20170633?PR
https://www.eurekalert.org/pub_releases/2017-07/rup-rdn071717.php

Nobel Prize 2016 in Physiology or Medicine

The 2016 Nobel Prize in Physiology or Medicine is awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy which was announced on 3rd October 2016

This year's Nobel Laureate discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components.

The word autophagy originates from the Greek words auto- meaning self and phagein- meaning to eat. Thus, autophagy denotes "self eating." Its a process whereby the eukaryotic cell can recycle part of its own content. This concept emerged during the 1960's, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack like vesicles that were transported to a recycling compartment, called lysosome, for degradation. Unlike other cellular degradation machineries, autophagy removes long lived proteins, large macro molecular complexes and organelles that have become obsolete or damaged. Difficulties in studying the phenomenon meant that little was known until, in a series of brilliant experiments in the early 1990's. Yoshinori Ohsumi used baker's yeast to identify genes essential for autophagy. He then went on to elucidate the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells.

Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease.

Yoshinori Ohsumi is a professor at the Tokyo Institute of Technology since 2009 

'Breakthrough' in malaria fight

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Australian scientists have identified a potential treatment to combat malaria.

Researchers in Melbourne believe their discovery could be a major breakthrough in the fight against the disease.
The malaria parasite produces a glue-like substance which makes the cells it infects sticky, so they cannot be flushed through the body.
The researchers have shown removing a protein responsible for the glue can destroy its stickiness, and undermine the parasite's defence.
The malaria parasite - Plasmodium falciparum - effectively hijacks the red blood cells it invades, changing their shape and physical properties dramatically.
Among the changes it triggers is the production of the glue-like substance, which enables the infected cells to stick to the walls of the blood vessels.
This stops them being pased through the spleen, where the parasites would usually be destroyed by the immune system.
Painstaking tests
The Australian team developed mutant strains of P. falciparum, each lacking one of 83 genes known or predicted to play a role in the red cell remodeling process.
Systematically testing each one, they were able to show that eight proteins were involved in the production of the key glue-like substance.
Removing just one of these proteins stopped the infected cells from attaching themselves to the walls of blood vessels.
Professor Alan Cowman, a member of the research team at the Walter and Eliza Hall Institute of Medical Research, said targeting the protein with drugs - or possibly a vaccine - could be key to fighting malaria.
"If we block the stickiness we essentially block the virulence or the capacity of the parasite to cause disease," he said.
Malaria is preventable and curable, but can be fatal if not treated promptly. The disease kills more than a million people each year. Many of the victims are young children in sub-Saharan Africa.