By Edwin L. Aguirre
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 the German-occupied Netherlands towards 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 health problems,” says Lee.
The impact of behavior and environment on gene function
In his latest research, Lee will use a specific type of roundworm, or roundworm, to study epigenetic changes that are passed down through many generations and help shed light on the impact of epigenetic inheritance on human health and disease. .
Although she considers her research 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. ‘man.
“Our genome – that is, our complete set of DNA – includes much more than just the genetic information of the DNA sequence itself; it turns out that the packaging of DNA in chromatin is important for controlling and regulating exactly when and how DNA is used, and therefore for gene expression,” says Lee.
Gene expression is the process by which information stored in our DNA is converted into instructions for making proteins and other molecules, enabling cells to respond to their changing environment.
“Like DNA, epigenetic information – that is, non-genetic influences on gene expression – is also passed from parent to child. But unlike DNA, chromatin can be both written and erased, which allows for much more nuance in the use of the genome,” Lee notes. “Mutations in the machinery that writes, erases, or reads epigenetic information have been identified in many types of cancers and in certain disorders severe human neurodevelopmental disorders.”
Tiny worms and longevity
Lee says studying epigenetic inheritance over multiple generations in humans, or even other mammals like mice, is difficult and time-consuming. An additional complication is that the researchers only identified a few traits that can be considered transgenerational, meaning characteristics that can be inherited for more than a few generations.
To overcome these challenges, Lee and his research team developed a novel model to study transgenerational epigenetic inheritance of chromatin using nematodes called Caenorhabditis elegans (or C. elegans, for short).
“These microscopic roundworms make an excellent 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,” explains Lee. “This means they are one of the few animals capable of producing truly genetically identical individuals.”
Lee adds that chromatin is such an important element in the control of gene expression, and therefore of all cellular functions, that most of the mechanisms involved in chromatin regulation are preserved, from complex organisms like humans to C elegans and even down to individual Yeast cells.
“Understanding how chromatin is maintained, regulated, or cleared across generations in C. elegans will shed light on what’s happening 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 several generations, progressively extended the lifespan of the worms by 20-40%.
“We had shown that this longevity was due to inappropriate epigenetic inheritance between each generation, which allowed the progressive accumulation of chromatin at the scale of the genome,” she says.
Lee will use his NIH grant to determine why this epigenetic inheritance affects lifespan and to better understand what information needs to be erased between generations to allow normal development.
“This is the first time such a study has been 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 want to understand how epigenetic information is normally reset with each new generation and what happens to individuals when this process goes wrong.
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 master’s student Cassidy Schultz.
“This research is well suited for undergraduate students – it’s easy for students to learn to work with C. elegans, so they collect real data very quickly,” says Lee.