Study Focuses on Genetic Information Passed Down from Generation to Generation

Biology Asst. Prof. Teresa Lee in the lab Image by Ed Brennen
Biology Asst. Prof. Teresa Lee works in her research lab at Olsen Hall on North Campus.

By Edwin L. Aguirre

Biology Asst. Prof. Teresa Lee’s research to understand what information is passed between generations, from parent to child, has been awarded a three-year, $374,000 grant by the National Institutes of Health (NIH).

Generational studies suggest that stress or trauma experienced by our ancestors can affect the health and behavior of subsequent descendants over multiple generations, according to Lee.

“For example, women who survived the Dutch Hunger Winter – a famine that occurred in German-occupied Netherlands near the end of World War II – were more likely to have children with obesity or type 2 diabetes, and their grandchildren also had a higher risk of obesity and other poor health outcomes,” says Lee.

The Impact of Behavior and Environment on Gene Function

Over the years, Lee’s research has focused on epigenetics, which is the study of how one’s behavior and environment can cause changes that affect the way that person’s genes function. According to the Centers for Disease Control, epigenetic changes are reversible, unlike genetic changes, which are not.

Nematode C. elegans_black and white
A microscope view of wild-type nematodes, or roundworms, called Caenorhabditis elegans. The adult worms measure about 1 millimeter in length.
In her latest research, Lee will use a specific type of nematode, or roundworm, to study epigenetic changes that are passed on over many generations and help shed light on the impact of epigenetic inheritance for human health and disease.

While she considers her research to be fundamental, she says there could be broad implications for the study of cancers and neurodevelopmental disorders, since mutations that affect epigenetic regulation increase the likelihood of these diseases and disorders in humans.

“Our genome – that is, our complete set of DNA – consists of much more than just the genetic information of the DNA sequence itself; it turns out that the packaging of DNA into chromatin is important for controlling and regulating exactly when and how the DNA is used, and therefore for gene expression,” Lee explains.

Chromatin is a mixture of DNA and proteins that forms the chromosomes found inside our cells. Our genome’s DNA is wrapped around cores of proteins, called histones, into a highly compact package to form chromatin fibers that make up the chromosome’s structure.

Gene expression is the process by which information stored in our DNA is converted into instructions for making proteins and other molecules, allowing cells to respond to their changing environment.

“Like DNA, epigenetic information – that is, non-genetic influences on gene expression – is also inherited from parent to child. But unlike DNA, chromatin can be both written and erased, which allows for much more nuance in how the genome is used,” Lee notes. “Mutations in the machinery that writes, erases or reads epigenetic information have been identified in many types of cancers and in some severe human neurodevelopmental disorders.”

Tiny Worms and Longevity

Lee says studying epigenetic inheritance over many generations in humans, or even other mammals like mice, is difficult and time-consuming. An added complication is the fact that researchers have identified only a few traits that can be considered as transgenerational – that is, characteristics that can be inherited for more than a few generations.

Nematode C. elegans_fluorescent Image by Natilia Woozencroft
This fluorescent image at 20 times magnification shows the roundworm’s DNA (cyan) and lipids, or fatty organic compounds (magenta). A single C. elegans can produce up to 300 eggs, which is one of the reasons Lee uses them for her genetics research.
To overcome these challenges, Lee and her research team have developed a new model to study transgenerational epigenetic inheritance of chromatin using nematodes called Caenorhabditis elegans (or C. elegans, for short).

“These microscopic roundworms make a great study system for this type of research because of their short generation time – they can produce a new generation every four days – and the fact that they are self-fertilizing hermaphrodites,” says Lee. “This means they’re one of the few animals that can produce truly genetically identical individuals.”

Lee adds that chromatin is such an important part of controlling gene expression, and therefore all cellular function, that most of the machinery involved in the regulation of chromatin is preserved, from complex organisms like humans to C. elegans and even down to single cells of yeast.

“Understanding how chromatin is either maintained, regulated or erased between generations in C. elegans will shed light on what occurs in many other higher organisms, including mammals and humans,” she says.

During Lee’s postdoctoral research at Emory University in Atlanta, she discovered two mutations in C. elegans that, over many generations, gradually extended the lifespan of the worms by 20% to 40%.

“We had shown that this longevity was due to the inappropriate epigenetic inheritance between each generation, which allowed for the gradual, genome-wide accumulation of chromatin,” she says.

Lee will use her NIH grant to determine why this epigenetic inheritance affects lifespan, and to better understand what information needs to be erased between generations to allow for normal development.

“This is the first time such study is being conducted,” says Lee. “In the short term, there are implications for human health and lifespan in understanding why these mutant worms acquire longevity. In the long-term, I’m interested in understanding how epigenetic information is normally reset with each new generation, and what happens to individuals when this process goes wrong.”

Collaborating with Lee on the project are UML Biology Asst. Prof. Frédéric Chain, who is conducting the genomic analysis, and Assoc. Prof. Michelle Mondoux of the College of the Holy Cross in Worcester, Massachusetts, for the lifespan and health analysis.

Several of Lee’s students are working on the project, including biology majors Deepshi Ananthaswamy, Natilia Woozencroft, William Miguel, Lea Solh and Michaela Dillon, as well as M.S. student Cassidy Schultz.

“This research is well suited for undergraduates – it’s easy for students to learn how to work with C. elegans, so they are collecting real data very quickly,” says Lee.