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  • Alex Cloherty

Recycling cells and hijacking viruses

The purpose of today's post is to explain what my research is about! I hope you enjoy reading about the fascinating subject of autophagy, and its two branches.

Let's start from the beginning. Like your apartment before you did spring cleaning, cells can also accumulate too much stuff. For cells, however, this is really a life-or-death scenario. The excess stuff in cells can be potentially dangerous, such as misfolded proteins. Remember, proteins are the machines within the cell – they do almost all of the work needed to keep a cell alive. If proteins are misfolded, i.e. incorrectly made, they might still do work, but do it the wrong way. You can think of this like a robot that is supposed to put away all of your clean dishes, but instead smashes them on the floor. As well as misfolded proteins, cells continually have to make new proteins and organelles, or cellular organs, to replace the old ones and stay healthy. To deal with all of this turnover of material within the cell, an elegant process of cellular recycling evolved: autophagy.

Autophagy, which translates to "self-eating" from Greek, is just that. Cells begin by wrapping up material that is no longer needed in a double-membrane structure made of fat, which kind of looks like two garbage bags layered inside one another. This structure is called an autophagosome. The autophagosomes, carrying material that needs to be recycled, go on to fuse with another membrane-bound structure inside the cell that carries acid and enzymes that break up stuff, kind of like a stomach. Once this fusion happens, the recycling inside the autophagosome is broken down, and the smaller pieces of it can be re-made into new proteins or organelles, in the same manner as what we humans do with our old plastic bags and cardboard boxes!

So, why is this a Microbial Monday post? Because sometimes, cells are able to use autophagy to recycle invading microbes! In the same way that they can recycle old proteins and organelles, some cells are able to recycle bacteria like Mycobacterium tuberculosis (causes tuberculosis), Salmonella enterica (Salmonella food poisoning), and Listeria monocytogenes (listeriosis). Some viruses, too, can be recycled this way. In fact, Dr. Carla Ribeiro, my supervisor, found recently that some human cells can actually degrade HIV this way! Of course, not all human cells can recycle HIV using autophagy - otherwise this virus wouldn't be so much of a problem for us. But, the fact that cells can accomplish this feat suggests that medication that targets autophagy could help with treating or preventing HIV infections.

To explain exactly what my research covers, there is one more thing you must understand. Classically, autophagy was thought to function only in this cellular recycling pathway. However, it was recently discovered that the same proteins and membranes that carry out the cellular recycling ("degradative autophagy"), have another role, too! The cellular machinery for autophagy can also function in getting stuff out of the cell: secretion. This branch of autophagy is called secretory autophagy.

A diagram of of secretory autophagy drawn by my talented little sister

A diagram of of secretory autophagy drawn by my talented little sister

There is some research already out on secretory autophagy. For example, it has been well-established that secretory autophagy is the process that releases some cellular messages to the outside of the cell. These cellular messengers are released if a cell detects unwanted things like bacteria, in order to alert other cells to the threat. Secretory autophagy might also be at the root of neurodegenerative diseases like Alzheimer's disease. Alzheimer's disease progresses because big plaques of sticky proteins form in the brain, and mess with the brain's normal functioning. In the last few years, more and more research has suggested that secretory autophagy is a mechanism by which cells throw up these sticky proteins out into the brain.

Now, this is really where I came in. My research asks if HIV and other viruses might be able to hijack secretory autophagy to escape already infected cells, and infect new cells. In the process, I'm also trying to uncover more of the details about how secretory autophagy works. I want to know which proteins are responsible for each step of the process: what folds the membranes around secreted material, what brings the secretory autophagosomes to the surface of the cell, and how exactly does the stuff in the secretory autophagosomes get from inside the cell to the outside? So far, I have more questions than answers… But that's just how research is supposed to start!

Until next week - do your recycling, too!

- Alex

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