Updated: Aug 31, 2018
If we take a look into any living cell, we would see a world a lot less organized than the pictures our science textbooks led us to believe. Instead we might see a massive army of different globs swimming around at breakneck speed, in a whole range of sizes and shapes. The globs seem to know where they’re going, and if you watch one for long enough you might even think it had a little brain of its’ own. Each one is like a tiny worker in a massive factory, racing to do its’ tiny job over and over again. It’s the kind of factory that Jeff Bezos dreams about.
Teeny Tiny Chaos
Each one of these globs is actually a protein, and they are the structures that do most of the active work inside any living cell. Wanna make new DNA? There’s a protein for that. Clear some of the trash all around the cell? Protein. Signal to against the wave of virus invaders? You guessed it, protein. Now, proteins are all built of practically the same material, which is primarily just 20 different little building blocks. MILLIONS of proteins exist in living things, and mostly all we have to work with is 20 shapes. Crazy, right? As you can imagine, everything must be pretty close to perfect so that the protein is functional. Each building block has intrinsic characteristics that make the protein fold into the exact shape of glob that can complete the task. Even single differences can have catastrophic effects! Have you ever noticed food packaging that said something along the lines of ‘Phenylketonurics: contains phenylalanine?’. Well, Phenylketonuria is a disease caused by a protein who couldn’t fold up properly because one single building block was one thing when it should have been another. Switch one block and boom, the whole organism has a debilitating disease.
Knowing how fragile each protein is, how can a cell protect itself? How can it possibly monitor millions of zooming globs to make sure each one is folded up correctly? That’s like noticing one persons’ belt buckle is loose at a sold out concert while standing on the stage. Mindboggling.
Keeping Disorder in Line
Dr. Kevin Morano, a researcher at UTHealth, is working with yeast to piece together part of the signaling system a cell may use. Dr. Morano’s work centers around something called the Heat Shock Response, which is a messaging relay cells use to pass around the knowledge that something may be wrong and ramp up production of the tools to fix it. Contrary to the name, the Heat Shock Response (HSR) is not only brought about by being too warm. In fact, the starting gun is generally a misfolded protein. The wonky worker is noticed by something called a chaperone (another protein), who floats around like a hall monitor, keeping an eye out and bringing all the proteins who can’t do their jobs to a trash recycling protein, where they’re broken down into the building blocks all over again. Single bad worker, small problem, easy fix. Dr. Morano’s current work focuses on situations where the problem is a lot bigger. The kind of problems where factory workers are keeling over left and right, alarms are blaring, and machines are pouring smoke. What happens then?
Proteins to the rescue. In the work Dr. Morano looks at, it goes like this: Chaperones are helper proteins, working both to carry signals and assist other proteins in getting where they need to go. One chaperone, called Heat shock protein 70 (Hsp70), is alerted to the problem by various alarms that something is going wrong. Having now heard this informational siren, it changes its own shape just a little bit, which passes the red alert along. Hsp70 is generally holding on tight to another protein called Hsf1 (Heat Shock Factor 1). Hsf1 is a protein that blocks the cell from manufacturing defensive tools unless their needed, saving energy for the cell. However, once alerted to trouble by the release from Hsp70, Hsf1 then to allows the cell to create the tools used to defend itself, cleaning up all the sick proteins before the whole factory goes up in flames. This is the Heat Shock Response in a nutshell: an all-out defense maneuver for when things start hitting the fan.
In the lab at UTHealth, researchers are looking at one type of signal that can raise the cells’ alarms, called oxidative stress. Proteins have to be held in a stable condition so that they don’t grab things they shouldn’t grab. When part of a protein gains or loses electrons, which can happen when something called a Reactive Oxygen Species comes along, the proteins get really handsy. They grab each other, they grab themselves, and either way the perfect glob shape has changed in a negative way. This is oxidative stress. Sometimes, we can even see a mob of the same protein all grabbing together and not letting go, and this is called an aggregate. Aggregates are some of the biggest problems behind diseases like Parkinson’s and Alzheimer’s Diseases, forming plaques of misfolded protein that end up in the brain. Dr. Morano looks at how oxidative stress flips a switch on the chaperone Hsp70, which is how it knows that the cell is in danger. Once the switch is flipped, Hsp70 can go to Hsf1, and Heat Shock Response can kick in to save the day.
Amazon warehouses have nothing on your cells.
Dr. Morano is a faculty member at UTHealth, as well as Dean of Faculty Affairs.