Dr. Ning Zhao
Assistant Professor
Department of Biochemistry and Molecular Genetics
How can we see what actually goes on inside of a cell?
Have you ever wondered what goes on inside of a cell? There are millions of molecules inside each cell in our body needed to carry out specialized functions. Dr. Ning Zhao leads a lab in the Department of Biochemistry and Molecular Genetics and she is fascinated with tracking individual proteins inside cells.
Let’s compare a cell to a beehive, where lots of worker bees are performing different duties to make the hive run efficiently, just like each protein in a cell is performing a different duty to keep the cell up and running. But what if you wanted to track one specific protein, or worker bee, from the time they were born, throughout their life all the way to its end? You might imagine this would be an incredibly difficult task to carry out among a huge hive of worker bees that all look very similar; this is also the case inside a cell with thousands of proteins bustling around doing various tasks.
Dr. Zhao has developed a new way to watch proteins inside cells!
While scientists have been able to look at different features of a cell in detail using a special type of microscope called a fluorescence microscope for the past 100 years, it’s been difficult to watch the life cycle of proteins inside a cell because scientists usually have to freeze the cell in time (by killing it, RIP little cell!) to apply the fluorescent dyes that tag the proteins and molecules inside the cells.
This is where Dr. Zhao comes in! She has spent her career focused on creating new tools to look at or visualize proteins inside live cells and track them over time.
Ning has developed a special tool called a ‘frankenbody’ to track specific proteins. Yes, you read that right, a frankenbody; a stitched together, tiny microscopy tool named after Frankenstein. Its created by stitching together pieces of protein that will target and bind to specific proteins inside the cell and allow scientists to visualize them because they light up when the microscope shines certain types of light on them.
So what exactly is stitched together to make the frankenbody?
You may have heard of an antibody before. Antibodies are made by specialized cells in your immune system to quickly target and bind to proteins that come from viruses and bacteria so that the body can identify and get rid of those invaders. Like the limbs stitched together to make Frankenstein, the frankenbody is made by stitching together the sticky parts of an antibody that tag a specific target (like an individual protein) with a structural scaffold (like the wooden frame that holds up a house) that is stable inside of a live cell and shines a colored light that scientists can see when it is bound to its target.
The Zhao lab uses and makes this kind of frankenbody tool to track proteins throughout their life cycle from birth to death. Proteins are dynamic, meaning they go through many different stages and forms throughout their lives. Frankenbodies can bind proteins with high specificity in all of the different forms that a protein might take. Part of Ning’s work has been focused on how proteins are folded just after they are created inside the cell. The process of making proteins is called translation. Translation is basically the birth of a new protein. Because proteins fold and take on three-dimensional shapes during translation (or birth), this kind of frankenbody tool is extremely helpful to track the protein as it changes forms.
This new and exciting ability to visualize protein folding during translation in a live cell is something that Ning and her lab are really excited to share with the research community here at CU Anschutz medical campus and beyond.
Why is tracking a protein through its life cycle so important?
A healthy cell needs to maintain a certain level of functional proteins at different points depending on what actions need to be accomplished within the cell. We call this protein homeostasis, which is the constant regulation of each stage of the protein’s life. Dysregulation in any stage of the protein life cycle could contribute to diseases like cancer, cystic fibrosis, Parkinson’s disease, Alzheimer’s disease and many more! Understanding protein regulation mechanisms can help us combat diseases by developing new therapeutics to help cells maintain their proteins in the proper forms throughout their life.
If you want to learn more about the scientist, please head to their official CU webpage.