In search of . . . genome organization: Rachel Patton McCord, PhD
On Tuesdays, the Daily Voice features a first-person narrative from a researcher explaining the science behind a recent grant, and the inspiration or impetus behind becoming a scientist at UMass Medical School. If you know of a researcher you’d like to see profiled, send an email to UMMScommunications@umassmed.edu.
My research in general is focused on the genome inside the nucleus of the cell, not only as a carrier of genetic information, but also as a physical entity that has a particular spatial organization and has to handle stresses and forces from within and without. If all the DNA in a human cell were stretched out end to end, it would be more than 3 feet long, so it is an interesting question how this long genome is folded and packaged to fit into the microscopic nucleus. We also know that proper three-dimensional organization of the genome inside the nucleus is important in biological processes such as regulating which genes are expressed in a given type of cell. So, disrupting this organization would likely have biological consequences. I am studying genome organization in the context of a few different types of physical disruptions that may happen in the life of a cell. First, I am investigating how the three-dimensional organization of the chromosomes affects the type of rearrangements (translocations) that may occur after DNA strands are broken by irradiation. I will also be studying how the genome structure is affected by and responds to the types of physical forces experienced by cells in our body. For example, how does the genome structure adapt or change when an immune cell has to squeeze itself through a blood vessel wall and to a site of infection?
Mistakes in a cell’s response to stress and damage in the genome can often lead to diseases. For example, translocations that occur after DNA breakage often give rise to certain types of cancer. My work investigating how genome organization affects these chromosomal rearrangements may help to explain the origin and progression of cancers that are caused or affected by rearrangements. Since all cells in the body experience various forces, measuring the effects of such forces and stresses on genome organization can help us to understand how forces on cells in human tissues and organs can affect their proper development and function. On a basic level, I will also be extending our scientific understanding of the way that genomes are organized in 3-D in different types of cells and the importance of this organization to fundamental biological processes.
Both of my parents are PhD scientists, so in a way, I came by my interest in science naturally. From the time I was very young, I always enjoyed any kind of puzzle, and so I was interested in the way that scientists and mathematicians approached large puzzling questions about the way the world works. In college, I was interested in many fields from biology and physics to music and religion. But when I found out about the field of biophysics, in which scientists use the approaches and concepts of physics and math to study and describe biological processes, I was fascinated. I was very intrigued by the idea that thinking quantitatively about cell and molecular biology could lead to new insights about how life works. In physics, it was very satisfying to learn about principles and equations that govern and describe natural phenomena and to be able to predict what would happen in a system according to these principles. Though biological systems are “messy,” I wanted to pursue the idea that similar principles could be discovered in biology using ideas from math and physics. I designed an interdisciplinary major in biophysics at Davidson College and continued in that direction in the biophysics graduate program at Harvard University. In addition to these “big ideas,” I enjoy the fact that in my work as a scientist, even minor daily tasks like writing a computer program to do a small piece of analysis or troubleshooting a minor aspect of an experiment continually provide interesting puzzles to solve.
I first came across the pioneering work that Dr. Job Dekker had done in the field of genome organization while I was in graduate school, and the interesting questions his lab was investigating at UMass Medical School inspired me to come and join their team. Job and his lab developed methods called 3C, 5C, and Hi-C, which have provided new ways to look in detail at the structure of the genome in the nucleus using molecular biology and sequencing techniques. Even though I have a long commute from Boston by train (so my husband and I can both get to our workplaces), the exciting research, inspiring discussions with colleagues, and access to expertise on a wide range of methods makes coming to UMass every day very worthwhile.
I think the most exciting part about the research that we are undertaking is the potential to gain a new understanding of the way a fundamental part of biology works. It is particularly meaningful when such a new understanding may have implications for complicated diseases like cancer. I am inspired by the fact that this research allows us to think about an aspect of biology in a new way: studying the genome in three dimensions instead of just as a one-dimensional string of letters. I am also excited by the possibility of new insights that come from combining approaches and ideas that have previously only been used in separate fields. Along these lines, I use both computational and experimental approaches in my work and always enjoy talking to other scientists in different disciplines.