Molecular Biologist

Ancient Viruses Gain New Functions in the Brain
Once thought to be little more than genetic junk, retroviruses lurking within host genomes have acquired new roles that may be involved in brain development, a recent study suggests
January 19, 2015 |By Andrea Alfano

About 8 percent of our genetic material is made up of absorbed forms of retroviruses.
Credit: National Cancer Institute
If thinking about the billions of bacteria taking up residence in and on your body gives you the wi***es, you probably won’t find it comforting that humans are also full of viruses. These maligned microbes are actually intertwined in the very fibers of our being—about 8 percent of our genetic material is made up of absorbed forms of retroviruses, the viral family to which HIV, the pathogen that causes AIDS, belongs.

Our intimate relationship with these so-called endogenous retroviruses may be distressing to think about but a study published last week in Cell Reports suggests that they may help shape that thinking by participating in brain development. By manipulating mice genetics, researchers found evidence that some endogenous retroviruses gained new roles that are important for brain development in our not-so-distant rodent relatives. “Brain cells are very complex compared to other cells,” says Johan Jakobsson, a researcher at Lund University in Sweden and lead author of the study. “Co-opting endogenous retroviruses allows for much more complexity, especially since they make up so much of the genome.”

Unlike other viruses, retroviruses contain only RNA and must insert all of their genetic material into their host’s DNA in order to reproduce. When this molecular hijacking happens in s***m or egg cells, the retroviruses can be passed down to the host’s offspring, who then pass them on to their offspring, and so on. Eventually, a combination of mutations and genetic policing detain the viral invader, preventing it from jumping to a new host or even making copies of itself. Many of the endogenous retroviruses in our genome have been imprisoned there for millions of years.

Most endogenous retroviruses serve a life sentence, and are essentially permanently locked down via a gene-silencing process called DNA methylation. The study by Jakobsson and colleagues suggests that certain endogenous retroviruses don’t serve such a harsh sentence and can get out on parole, so to speak, to carry out important developmental duties in the brains of mouse embryos.

The parole officer in this situation is a protein called TRIM28, which has the ability to put the endogenous retroviruses back on lockdown by a more reversible gene-silencing process, called histone modification. After researchers knocked out TRIM28 in a variety of cells, including liver, brain and white blood cells, they noticed changes in mouse gene expression only in brain cells. “There seems to be a different mechanism regulating endogenous retroviruses in brain cells than in other cells,” Jakobsson says.

Furthermore, reducing the abundance of TRIM28 by deleting only one of the two copies of the gene that encodes it resulted in hyperactive mice. This isn’t enough to conclude that endogenous retroviruses are responsible for these behavioral changes, but taken together with the other findings of this study, they are likely suspects. “This paper provides evidence that endogenous retroviruses play an active role in gene expression in the brain through a dynamic mechanism,” says Guia Guffanti, assistant professor of clinical neurobiology at Columbia University, who was not involved in the study. In this way endogenous retroviruses may help brain cells more intricately regulate their gene expression, thereby allowing them to become more complex.

Determining exactly what these endogenous retroviruses are doing during their periods of limited freedom will require more research, but these experiments suggest that they are somehow involved in brain development—and that is already more than they were once thought to be capable of. Endogenous retroviruses are part of a larger class of genetic material, called transposable elements, that were and often still are dismissed as genetic junk that does little more than take up space in the genome. Studies like this one are slowly changing this assessment. “This brings a completely new perspective on what transposable elements can generate,” Guffanti says.

http://www.sciencedaily.com/releases/2015/02/150212183513.htm

New mechanism that controls immune responses discovered Researchers have identified a common signaling mechanism to produce interferon -- one of the main proteins used to signal the immune system when the body needs to defend itself against a virus, tumor, or other diseases.

http://www.sciencedaily.com/releases/2015/02/150212153947.htm

Molecular 'switch' that regulates DNA replication and transcription Researchers have discovered a molecular ‘switch’ that controls replication and transcription of mitochondria DNA, a key finding that could influence the development of targeted therapies for cancer, developmental processes related to fertility and aging.

New technique identifies protein production in specific cells at specific times
Published on 17th April, 2014 Copyright © 2014 MRC Laboratory of Molecular Biology.
chin_insight_4-14_215Research undertaken by Jason Chin’s group, in the LMB’s Centre for Chemical and Synthetic Biology (CCSB), part of the Protein and Nucleic Acid Chemistry Division, has successfully developed a novel and versatile technique to identify proteins produced in a particular set of cells at a particular time.

Individual sets of cells in the body of an animal are specialised to do different things. To gain insight into many biological processes, it is important to understand the differences between cells in the body. One key thing that differs between cells is the set of proteins they produce. Identifying the proteins synthesised at specific times in cells of interest is vital in helping to study cellular functions and dynamic processes.

Work, led by Tom Elliott, Fiona Townsley and Ambra Bianco, has led to the development of a method to tag the proteins in specific cells in the body produced at particular times. Using Drosophila melanogaster, the common fruit fly, as a model organism they have incorporated unnatural amino acids into proteins in order to label, image and identify proteins in specific cells in a developing fly under physiological conditions. They developed an approach that takes the way cells normally make proteins and added a ‘highlighter’ to the proteins synthesised in particular cells, so that proteins from just those cells light-up. This groundbreaking method allows us to define the proteins produced in specific cells at specific times. It is the first time that tagging of proteins from defined sets of cells in a whole fly has enabled the identification of proteins produced in a particular set of cells at a particular time.

The development of this novel and versatile technique involved a very broad interdisciplinary approach, and the method has the potential to become widely used in many different fields.

This work was supported by the Medical Research Council and the European Research Council