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  • NIH awards IU biologist $1.66 million to study chromosome biology

NIH awards IU biologist $1.66 million to study chromosome biology

Tuesday, March 9, 2021

Xindan Wang.
Xindan Wang. Photo by Sandee Milhouse

The National Institutes of Health has awarded a biologist at Indiana University Bloomington a grant to study chromosome biology.

Xindan Wang, assistant professor in the IU Bloomington College of Arts and Sciences' Department of Biology, will receive $1.66 million from the National Institutes of Health's Research Project Grant Program (R01) to study chromosome organization and segregation. Support from this award will officially begin on April 1, 2021.

All living cells contain long strands of DNA molecules that are packaged into chromosomes. When cells grow, chromosomes are duplicated and transmitted to daughter cells. The faithful segregation of chromosomes underlies genome integrity and is fundamental to all organisms.

“No reproductive process is more central to life than the replication and segregation of the genome,” said Wang, who joined IU Biology in 2017. “The goal of our research is to identify the molecular mechanism of chromosome segregation. Our studies have the potential to uncover the general principles of chromosome packaging and segregation relevant to all domains of life.”

Wang’s research focuses on a protein complex called the structural maintenance of chromosomes (SMC) complex, which is highly conserved from bacteria to humans. Recent studies show that SMC complexes are motors that track on DNA strands. Using bacteria as model systems, Wang’s research will investigate the mechanism of SMC action in the context of cellular activities. Her team will combine molecular biology, cell biology, biochemistry, and genomics approaches to determine how SMC gets on and off the DNA, and how SMC resolves conflicts with other cellular machineries.

Bacillus subtilis cells (blue) show unsegregated DNA (red) and replication origins (green) in the absence of the SMC complex.
Bacillus subtilis cells (blue) show unsegregated DNA (red) and replication origins (green) in the absence of the SMC complex. Image courtesy of Xindan Wang

“Our work will shed some light on the general principles of chromosome folding and compaction in all organisms,” said Wang. “Understanding these processes will tell us how genetic information can be faithfully transferred from one generation to the next. This is a fundamental aspect of life.”

The team of experts collaborating with Wang on this grant includes three IU Bloomington faculty members—Julia van Kessel (College of Arts and Sciences' Department of Biology) for a novel method to identify new interacting proteins, Clay Fuqua (College of Arts and Sciences' Department of Biology) for microbial genetics and physiology, and Martha Oakley (College of Arts and Sciences' Department of Chemistry) for biochemical interactions—as well as Leonid Miry (MIT) for mathematical modeling of experimental data and HyeongJun Kim (University of Texas Rio Grande Valley) for single-molecule experiments.

The most recent work from Wang’s laboratory has been published in Molecular Cell. The first author, Xheni Karaboja, did the work when she was a research associate in the Wang Lab. Karaboja is now a first-year Ph.D. student in the Microbiology Graduate Program at IU Bloomington. The second author, Zhongqing Ren, is a third-year Ph.D. student in the Genome, Cell, and Developmental Biology Graduate Program.

Presented here is the overlay of eight Hi-C contact maps showing that DNA alignment by SMC complexes do not pass the terminus region irrespective of the position of SMC complexes’ loading sites.
Karaboja, et al. show that SMC complexes are unloaded at the replication terminus by the recombinase XerD. Image courtesy of Xindan Wang
Karaboja Xheni.
Xheni Karaboja. Courtesy photo
Ren Zhongqing.
Ren Zhongqing. Courtesy photo
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