The human body is a complex machine. What adds to this complexity is that everything in your body is interconnected, each part impacting multiple other parts.
We see this in practice when people’s blood vessels regrow after a heart attack, avoiding the previously damaged area. This is one example of the highly adaptive nature of the human body.
This level of complexity is mirrored on a much smaller scale, between and within your cells, which are the smallest parts of every organ in your body. When cells need to communicate, there often isn’t just one cell sending one specific message, but several cells sending different messages that must be understood by target cells. This flexibility allows the body to adapt in case a single part breaks down.
However, this same complexity can act as a double-edged sword. The more parts there are, the more are the chances of multiple parts breaking, resulting in disease. One such multipart system is called the kinase network and is the focus of my research.
Kinases are special proteins in the human body that are important for transmitting signals both between cells and within a cell. Kinases transmit information by using special molecules that they pass on to the next kinase in the chain. This is like a relay race where multiple humans (kinases) are transferring a single flag (molecule) to the next one in the chain. At times, the kinase chain splits, when one kinase transfers the message to two or three different kinases. This double or triple message system is to make sure the message is passed on to the target cells.
My research project is to identify these kinase networks in a given disease and how they change in this disease. The idea behind this is that if we can identify what a normal network looks like and what changes in the presence of a disease, then we can then identify the key central kinase. Once we identify the central kinase, we can then work on restoring the original network function, hopefully restoring the normal function of the cell.
My process to achieve this goal is to first collect cells from both diseased and normal sources. I then put them in a machine that is called a kinome array. This kinome array machine is able to look at all the kinases that are inside the cells and their messaging activity. The results of the kinome array are a series of pictures, with bright lights on a dark background. The more active a kinase is, the brighter its light and the more visible it becomes. I then take each level of brightness and convert that into numbers that I can work with, called data.
Once I have all the data, I use a supercomputer to carefully analyze it. This process allows me to look at the times when one kinase’s activity goes up and another kinase’s activity either goes up or down at a similar rate. This lets me identify if these two kinases are related. I do this for all possible pairs of kinases that are in my data and then simplify this into a relationship map. The relationship map looks like series of circles connected by arrows.
Imagine this is an actual map, with the circles representing cities and the arrows representing freeways that are connecting those cities. In our case, the freeways are one-way only. You can only go in one direction on them and not the other way. What this means is that once you leave a city, there’s no way to get back to the city.
We are now using this method to work on more ways to treat schizophrenia. This is allowing us to identify how there might be kinase network changes in the brain and then identify what kind of medication can return that network to normal function.
This kind of research is instrumental in identifying how diseases occur and how they can be treated. With the use of instruments like kinome arrays and the software that can be run on super computers, we can quickly identify causes of diseases and targets for drugs. With this research approach, research progresses by leaps and bounds. The goal of my work is to make sure that we keep expanding these methods and make the work easier for my fellow researchers in every field.
Ali Imami is earning his PhD in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Ali is doing his doctoral research in the laboratory of Robert Mccullumsmith, MD/ PhD, in the Department of Neuroscience. For more information, contact Ali.Imami@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical
First Published March 1, 2021, 12:30 p.m.
