[Guest post] Tit for tet: Tet3 regulates neuron activity through epigenetic changes

Please welcome Eat, Read, Science’s first guest blogger Julia Turan! Today she’ll be sharing a cool new paper looking at how changes in our DNA change the way our neurons talk to one another.

Sequence the human genome. Check. Now all that’s left is to understand how the letters of our DNA alphabet are accessed in the context of different types of cells and microscopic environments. Completing the sequence was no small feat but we have plenty of work ahead. This field is known as epigenetics: the study of factors—inside or outside our body limits—that turn genes on or off and influences how our cells read the genome.

Nature and nurture. Two words frequently tossed around in biology. Epigenetics takes these formerly opposing concepts and swirls them together. Our nature is being nurtured. Our experiences are altering the expression of our DNA. Really let that sink in.

A term coined by C.H. Waddington (known as ‘Wad’ to his friends) in 1942, epigenetics was first studied in embryonic development. As we morph from wad to body (pun intended), cells with the same DNA blueprint become part of team lung, blood, brain, etc. Epigenetic mechanisms control this differentiation of cells. There are two important traits of these changes: 1) the DNA sequence is not directly altered, rather its expression—how it is read out and turned into a protein—is; and 2) these changes can persist after the cell divides and even in the organism’s progeny.

Thanks to Hongjun Song and his team at Johns Hopkins University, we now know that experience also influences genetic expression in the incredible three-pound clump beneath our skulls. Their research showed that these changes don’t just happen during stress, aging or neurodegenerative diseases. They are happening in all of our brains at this very moment. The chemical structure of the DNA in your brain is actively regulated in response to what you’re experiencing. These processes are essential to the stability of our brain circuits and potentially its disruption during disease. Continue reading

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Introducing Lassa-VSV, a hybrid virus that kills brain tumours

Electron microscopy image of vesicular stomatitis virus particles (Image: Dr. Frank Fenner)
Electron microscopy image of vesicular stomatitis virus particles. The bar represents 100 mm. (Image: Dr. Frank Fenner)

Last month, I wrote about using Salmonella to deliver anti-cancer compounds to tumours. Today, I’m sharing with you a paper on cancer-fighting viruses. Why the recent focus on microbiology and cancer? Because they’re much more interconnected than you would think and because they’re both so cool! (And maybe also because I’m a microbiologist and my husband is a cancer geneticist so it’s kind of like a mash-up of us.)

By now, most people will have heard of viruses that can cause cancer, the most well known example being human papillomavirus (HPV) and cervical cancer. But did you know that some viruses can also destroy cancers? These oncolytic viruses infect cancer cells and hijack the cell’s machinery to make lots and lots of new viruses. Eventually, the cancer cell becomes so full of viral progeny that it bursts open and dies. In doing so, it releases its cargo of oncolytic viruses to infect neighbouring cancer cells. When these viruses infect normal, healthy cells, the cells use their anti-virus immunity to prevent the invaders from taking over their machinery and making new viruses. In cancer cells, these anti-virus immune systems are weakened or disabled, giving the viruses free rein over the cells’ resources.

Vesicular stomatitis virus (VSV) is particularly good at attacking tumours. In preclinical studies, VSV has been successful in targeting a number of different cancers, including cancers of the prostate, breast, liver and colon. Furthermore, VSV has shown great potential in treating brain tumours, a disease for which treatment options are limited and prognoses are typically poor. One of the major obstacles to using VSV to destroy brain tumours is safety. While VSV preferentially targets and kills tumour cells, it also attacks normal brain cells, leading to harmful effects on motor coordination, behavior and other neuronal processes.

The neurotoxic effects of VSV seem to be primarily caused by a special protein on the surface of the virus, known as a glycoprotein or G protein. In a paper published this past week in the Journal of Virology, researchers at Yale University and Harvard University tried to overcome the neurotoxicity of VSV by engineering a hybrid virus. The researchers wanted to know if swapping out the G protein of VSV with the G protein from another virus would lessen the harmful effects of VSV on the brain while maintaining its tumour-killing abilities. Continue reading