In the second installment of our Ten-hundred word challenge, inspired by the Up Goer Five xkcd.com comic, we explore the inner-workings of biology. Our writers take a crack at simplifying their research on how immune cells target and kill cancer cells, and why muscle proteins have been found in brain and ear cells. As always, we hope you have fun and learn a little from our light-hearted attempts at reducing highly advanced scientific research to the vocabulary of a five year old.
Your body is made of bags of water packed together. Some bags of water can change, making them grow too much and making you sick. Other bags of water that live in the blood work as guards to protect the body. These guards find sick parts or bags that grow too much and kill them, keeping you well. How? The guards see (really, touch) signs of a problem on the outside of the sick bags and stick to them. Then, the guards throw out small things that attack the sick bags. We don’t know how those things enter the sick bags, or how they work inside to kill the sick bags without hurting anything else in the body. I want to find out how those attack things get inside the sick bags. In order to learn about this, I use small sick bags grown on a plate and study what happens after mixing guards into the soup in the dish.. So, first I make sick bags with many different changes inside. Then, I put the guards next to the sick bags and wait, keeping only those sick bags that live through the attack. Last, I read the still-living sick bags to learn about which changes inside are most important for living or dying in an attack from the guards. So far, I’ve learned which of many signs on the outside of the sick bags are important for guards to touch them and attack. I still need to learn about how the attack pieces work inside the sick bags, though. This might help us understand how the body changes to escape the guards when we get sick.
A subset of immune cells, known as T cells and Natural Killer cells, can eliminate infected or cancerous cells in the body. These immune cells distinguish between healthy cells and those that should be targeted for destruction by interacting with many surface proteins. The immune cells can then form a brief but stable attachment to the target cell. After attachment, the immune cell releases cytotoxic proteins that get taken up by the target cell, ultimately causing the target cell’s death. While immune cells can use multiple pathways to kill identified targets, cytotoxic molecules are one of the most important – and we don’t know exactly how they enter the target cell, or how their movement and activity in the target cell is regulated. In order to study this process, I use genetic screens in cultured human cancer cell lines with genome-wide mutations. Using a model immune cell line that kills these cancer cells, I can select for mutations that increase target cell survival. Then, I use high-throughput sequencing to “read” which mutations are most prevalent in the surviving cell population. I’ve identified surface proteins important for recognition by the immune cells, but am still developing a system to specifically study cytotoxic protein uptake and activity. Learning which genes and processes in target cells are required for cytotoxic protein uptake might ultimately provide insight into cancer progression and immunotherapy.
Your body is made up of lots of small parts. Some of these small parts allow you to move around, go from place to place by moving your arms and legs, and lift things off the ground. These smaller parts are made of even tinier things. These tinier things are usually only found in the parts of your body that allow you to move. However, I found one of these tinier things in the brain! To figure out what this tinier thing is doing there, I will make an animal that does not have this thing. To do this, I will cut out a small part of the animal’s body-directions before it is a baby and then watch it grow up. I think that without this tinier thing, the animal will not move very well and might have bad hearing.
Muscles are mostly made of proteins known as myosin heavy chains. There are many types of myosin heavy chains, but only certain varieties are in muscle tissue. These proteins provide the structure and force to drive muscle contraction. Unsurprisingly, these muscle-specific myosin heavy chains are found in our hearts and skeletal muscles. However, one of these muscle myosin heavy chain proteins was recently found in brain tissue and in ear cells! To figure out what this muscle myosin heavy chain protein is doing in these abnormal locations, I will make a knockout mouse model. Using genome-editing, I will delete the gene that controls the expression of this protein. Because this protein is normally expressed in parts of the brain that control motor coordination and auditory processing, I suspect that the knockout mice will exhibit uncoordinated movement and hearing loss.