Upasna Sharma, assistant professor of molecular, cellular, and developmental biology at UC Santa Cruz, received a $ 1.18 million grant from the John Templeton Foundation to support her research into how life experiences and a father’s environment can influence the health and well-being of his children. .
A growing body of evidence supports the idea that a person’s environment, including things like diet and stressful experiences, can influence the health and longevity of their descendants. These effects are not the result of mutations or other genetic changes in DNA transmitted in chromosomes, but are believed to be mediated by “epigenetic” factors that alter the way genes are expressed.
Sharma has conducted pioneering research into the mechanisms of this phenomenon, known as ‘transgenerational epigenetic inheritance‘, focusing on how a father’s lifestyle or experiences can affect the development of his children. . In studies on mice, she found that when males are given a low-protein diet, their offspring can have metabolic disorders that affect their development. What’s more, his research indicates that information about a male’s diet is transmitted to his sperm via small molecules of RNA.
The new grant will fund Sharma’s efforts to provide a detailed molecular explanation for these observations. This project aims to provide a first in-depth understanding of the key stages involved in the transgenerational epigenetic inheritance of the father’s life experiences and environment.
“Determining the mechanisms of transgenerational inheritance has important implications for public health and policy,” said Sharma. “Many common metabolic diseases, such as diabetes, have both genetic elements and contributions from a patient’s lifestyle and environment. Only a fraction of the heritability of these diseases can be explained by genetic variation; instead, it is now increasingly appreciated that epigenetic inheritance probably contributes to such diseases. “
Recent findings have challenged pre-existing notions about the inheritance of acquired traits, that a hypothetical barrier, known as the “Weissman barrier,” prevents the transmission of information from somatic cells (the non-reproductive cells of the brain). body) to germ cells (eggs and sperm).
“There is now a ton of data from different labs that supports the transmission of paternal environmental effects to offspring, but the mechanism remains a mystery,” Sharma said.
His previous studies indicate a possible mechanism, suggesting that a subset of small RNA molecules in mature sperm are not synthesized by the germ cells that produce sperm, but are instead made in the cells of the epididymis, a long, convoluted tubule where sperm mature. after their production in the testes.
“Sperm carry very little RNA, especially compared to the egg, so a question is, is sperm RNA transferred to the embryo during fertilization and contribute to embryonic development? “
To answer this question, she plans to generate “tracer” RNAs that she can use to monitor the transmission of small RNAs from somatic cells from the epididymis to sperm, and from sperm to the embryo. Sharma will also study whether environmental disturbances cause changes in the small RNAs produced in the epididymis and transmitted to sperm. Another important question she will address is whether these changes are passed on to all sperm or only a subset of them.
“We want to determine if all sperm are the same when it comes to the epigenetic effects of environmental stressors,” Sharma said. “This is important to know because only one sperm fertilizes the egg, so the effects may not be seen in all offspring. “
Sharma received the NIH Director’s New Innovator Award from the National Institutes of Health in 2019 and a Searle Scholars in 2020. She joined UCSC faculty in 2018.