The National Institutes of Health (NIH) has a grant program that provides promising NIH fellows with the research support and mentorship they need to land permanent academic research positions. Known as a K99-R00 award, the NIH Pathway to Independence Award has helped many postdocs boost their careers. Now, two more NIEHS fellows, Joonas Jamsen, Ph.D., and Fei Zhao, Ph.D., can add their names to the growing list of recipients.
DNA repair and disease
Jamsen uses biochemical and biophysical techniques to understand how certain enzymes, known as DNA polymerases, assemble DNA. He said members of the X-family of polymerases — polymerase beta (pol beta), polymerase lambda (pol lambda), and polymerase mu (pol mu) — are essential for life, because they help repair DNA.
But sometimes they incorporate damaged molecules during the DNA-building process. One of the most common damaged molecules is called 8-oxo-G, and Jamsen wants to understand how it can lead to cancer and other diseases.
When Jamsen came to NIEHS in 2014, members of the DNA Repair and Nucleic Acid Enzymology Group, led by Samuel Wilson, M.D., were using a new technique called time-lapse crystallography to see chemical reactions that take place in the cell. They used that method to observe how pol beta repairs damage and inserts 8-oxo-G. Jamsen’s K99-R00 grant takes that research a step further.
'Pol lambda and pol mu are distinct from pol beta, so I want to determine their similarities and differences compared to pol beta,' Jamsen said. 'My research will reveal how environmental agents, such as radiation or toxicants, impact how polymerases work.'
Battle of the sexes
Zhao studies fetal development of reproductive organs, specifically the reproductive tract. He said he was proud that his work with mentor Humphrey Yao, Ph.D., and the rest of the NIEHS Reproductive and Developmental Biology Group, led to a groundbreaking discovery.
They found that normal female mouse embryos, which produce a protein known as COUP-TFII, have a female reproductive tract. In contrast, female mouse embryos without COUP-TFII contain both female and male reproductive tracts. It appears that the protein actively promotes the removal of the male tract.
For his K99 proposal, Zhao explained that although the male reproductive tract disappears in female embryos during differentiation, some of the male tract remains and contributes to the female reproductive tract. He plans to continue to study the development, function, and pathogenicity of male tract residue cells in the female tract.
He said the experience of writing a K99/R00 was invaluable, and young researchers interested in an academic job should try it. 'Whether you receive it or not, it helps you develop good grantsmanship,' Zhao said.
Yao highlighted other strengths Zhao brings to his work. 'With Fei’s creativity and work ethic, I am confident he will be successful no matter where he goes.'
Jamsen and Zhao both said they were grateful to the many people who participated in fruitful discussions, which helped them craft their research proposals. As with other K99/R00 awardees, they will receive funds for up to two years of mentored research here at NIEHS, and when they start their own labs somewhere in the United States, the R00 grant will pay for three years of research.