Inspired by this XKCD Up-Goer Five comic (and aided by this Up-Goer Five text-editor), we present three cases of complicated science made… simpler. This installment is a Biochemistry Edition! Graduate students Kelsie Anson, Graycen Wheeler and Adrian Ramirez describe their research only using the 1,000 most common English words.
Your brain is made up of lots of little brain blocks. These brain blocks pass notes to their friend brain blocks. These friends eat the tiny notes and use them to decide if they need to move, grow, or make new tiny notes.
I want to know how the friend blocks read these tiny notes and decide what to do next. I am also interested in how what we eat can change the way brain blocks read and write notes to their friends. I use color and light to look at the tiny notes that brain blocks send to each other. To do this I put little lights in brain blocks that change colors when a note is there. When the brain blocks send notes, this light will change color or move and I can watch it with a special eye glass.
This tells me that some of the things we eat are important for brain notes getting to the right place and for brain blocks reading the right information. This helps us understand all the ways brain notes work together to let us learn and remember.
Less simplified explanation
All cells use signaling molecules to make decisions and communicate. Neurons release signaling molecules called neurotransmitters to communicate between cells, and a particular subset of neurons in the hippocampus also release the metal ion zinc along with the standard neurotransmitters. Very little is known about why zinc is released or what it does. Importantly, cells have lots of zinc that is bound to proteins, but I am mostly interested in how neuron signaling changes the amount of free zinc in a cell that is available to bind to new proteins. I then study how this free zinc interacts with other signaling molecules to change how these neurons grow and make new connections. This is crucial because many of the neurons that release zinc are very important for learning and memory.
The main tool I use to study this is a sensor that detects free zinc in cells using a zinc binding domain fused to blue and yellow fluorescent proteins. The yellow protein does not emit light on its own, but it accepts energy from the blue protein when they are close together. When zinc binds to this sensor, the zinc-binding domain brings the two fluorescent proteins close together and you see more yellow fluorescence. The ratio of yellow to blue can then tell us how much free zinc is in the cell. It also shows us how zinc changes over time or differs in certain parts of the cell.
These cells (above) are expressing a zinc sensor, and the color is based on the ratio of yellow to blue fluorescence, with warmer colors indicating that there is more zinc bound to the sensor. To calculate how much free zinc is in each cell I also need to know how tightly my sensor binds zinc and the maximum and minimum possible yellow-to-blue ratio.
Your body is made of many tiny life blocks. Sometimes a few of your life blocks go bad. They start growing too quickly and try to take over your body. This makes you very sick. Doctors try to help by giving you little circles to eat that kill the fast-growing blocks and leave the normal ones alone. Most of the time, these circles work for a while until the bad blocks learn how to avoid them. Then not only do you get sick again, but also the bad blocks are stronger and harder to stop.
Life blocks (especially the bad blocks that want to take over) are always making machines that help them live. I think that the bad blocks are making special life machines to keep them strong and safe. Somehow, the bad blocks know when we are trying to kill them and choose to make more special life machines. How do they know? What exactly does the new life machine do? If we can figure this out, maybe we can confuse the bad blocks so that they stop making machines that keep them safe. Then we can stop them from making you sick, and you can be happy and okay.
Less simplified explanation
Scientists have worked incredibly hard to develop an arsenal of powerful cancer drugs. These drugs are quite effective at killing cancer cells initially, but many tumors develop resistance and survive drug treatment. I study a protein that may play a very important role in this drug resistance. Very few researchers study this protein, so we don’t know very much about it. We do know that it helps cells survive, especially cancer cells.
When I treated colon cancer cells with a cancer drug, I noticed that the cells made much more of this survival protein. I wanted to know if other drugs might be causing cells to express more of this survival protein. To test this, I treated cells with 100 different FDA-approved drugs and measured how much of this survival protein they made. This experiment showed that many commonly-used cancer drugs cause cells to express more of this survival protein.
This phenomenon may be making drug treatments less effective, and it may be very important for drug resistance in general. I am trying to understand exactly how cells recognize drug treatment and signal to upregulate this survival protein. If we can understand this process, we can create tools to prevent cells from expressing this survival protein. Understanding the survival protein’s downstream signaling could also help us minimize its pro-survival effects, thus more effectively killing cancer cells.
Your brain, like the rest of your body, is made of small bags of life. These little bags work because of littler power machines that give your bags of life the power they need to live. When these little power machines in your brain get hurt, your brain can die or make your body sick. There are helpers that keep these little power machines working right. They can fix the power machines when the power machines are broken. When the little power machines can’t be fixed, the helpers clear the broken machines out so that other bags continue working. We want to figure out exactly how these helpers know which little power machines to fix, how they know what the problem is, and how they begin fixing. If we can understand how these helpers work, we can figure out ways to keep your little machines alive so that your bags of life and your brains stay well.
Less simplified explanation
Neurodegenerative diseases, or diseases in which brain function declines, are an increasing problem in today’s aging society. Mitochondria, the powerhouses of the cell, can cause several of these diseases when they are dysregulated. I study a biochemical pathway, or series of interacting proteins, that is important for regulating mitochondrial function. The proteins in this pathway can sense and tag damaged mitochondria. A mitochondrion that is “tagged” will be sent to a different part of the cell and be degraded. The genes for some of the proteins in this quality control pathway are mutated in a number of Parkinson’s Disease patients. By better understanding these proteins and the mutations that impair them, we gain insights into how cells deal with impaired mitochondria. In the future we might also be able to design treatments for patients who have these particular disease-causing mutations.