Dmitri A. Nusinow

Dmitri Nusinow is an American chronobiologist who studies plant circadian rhythms. He was born on November 7, 1976, in Inglewood, California. He currently resides in St. Louis with his wife and two children, and his research focus includes a combination of molecular, biochemical, genetic, genomic, and proteomic tools to discover the molecular connections between signaling networks, circadian oscillators, and specific outputs. By combining these methods, he hopes to apply the knowledge elucidated from the Arabidopsis model to other plant species.

Education and career

Early life Dmitri (Meter) Nusinow grew up in Los Angeles, and as a high schooler, he was inspired by the potential that genetic engineering had to change lives through medicine and food security. Nusinow received his bachelor's degree in Microbiology and Molecular Genetics at University of California Los Angeles (UCLA) in 1998. After he graduated from UCLA, Nusinow worked in Dr. Jay Gralla 's lab from 1998 to 1999 and studied in vitro analysis of RNA Pol II transcription in the fission yeast, S.pombe. He continued his education to earn his PhD in early mammalian development Her research paper was titled "Testing conservation of circadian clock genes in Arabidopsis Thaliana and Setaria Viridis." They are interested in determining how plants are controlled by light and temperature to predict how they respond to a changing environment with climate change. In 2021, Nusinow and fellow researcher Xuemin (Sam) Wang were awarded a $1.2 million grant from the National Institute of General Medical Sciences for their project, titled “Unraveling the molecular connections that link circadian rhythms and lipid metabolism.” This project aimed to explore the interplays between the circadian clock and lipid metabolism using Arabidopsis thaliana as a model organism, with the goal of understanding how these regulatory mechanisms have far-reaching implications for human health.

Nusinow has also been recognized for mentoring emerging scientists. Under his guidance, Sarah Pardi, a PhD student in his lab, was named the 2024 William H. Danforth Plant Science Fellow, an award recognizing graduate students who demonstrate exceptional potential to advance the field of plant science. Pardi's selection highlights the mentorship and training provided in Nusinow's laboratory.

Scientific contributions

RNA Pol II Transcription As a research associate in the Gralla lab at UCLA, Nusinow co-authored a study published in the Journal of Molecular Biology investigating the role of general transcription factors in RNA polymerase II transcription initiation. They explained that Xist RNA is necessary and sufficient for initiating and spreading silencing to inactivate one X chromosome (Xi) in females for dosage compensation. Xist RNA is encoded in the X-inactivation center (Xic), and cis-regulatory elements (CREs) on the Xistgene regulate its expression and activity while the X chromosome to be inactivated is selected. Xist RNA also coordinates chromatin modifications that maintain the inactive state of the Xi.

Histone Variant macroH2A1.2 and Gene Silencing For his graduate thesis at the University of California, San Francisco, Nusinow characterized the histone variant macroH2A1.2, identified through novel post-translational modifications. He demonstrated that the histone domain of macroH2A1 contains multiple discrete regions sufficient for its enrichment in heterochromatic regions and on the inactive X chromosome (Xi), where it helps maintain gene silencing. He used tandem mass spectrometry to study covalent modifications on macroH2A1.2, confirming the presence of several modifications on endogenous macroH2a1.2. Such modifications may be highly relevant for regulating chromatin binding and structure.

Nusinow also established a functional link between macroH2A and Poly (ADP-ribose) polymerase 1 (PARP-1). PARP-1 is an enzyme involved in modulating chromatin structure, regulating gene expression, and repairing DNA. MacroH2A1.2 interacts with PARP-1 via its non-histone domain (NHD), which inhibits PARP-1 enzymatic activity in vitro. He demonstrated that macroH2A's inhibition of PARP-1 is crucial for maintaining chromatin silencing, especially at the inactive X chromosome. These findings suggest that macroH2A contributes to heterochromatin formation and transcriptional repression through recruitment and inhibition of PARP-1. This complex plays a vital role in maintaining the plant's circadian rhythms by coordinating gene expression patterns that peak at dusk. Nusinow and his team demonstrated that the EC functions as a transcriptional repressor, controlling the expression of target genes that regulate growth and flowering in response to day length and temperature changes.

They became interested in FKF1 and GI because both proteins showed peak levels of activity at the same time during long daylight periods. To understand how these proteins might work together, the researchers first isolated them in a test tube. They found that blue light caused FKF1 and GI to form a complex (or bind together). This happened because FKF1 has a special region called the LOV domain that can absorb blue light, and GI has a part at its beginning (the N terminus) that can attach to FKF1.

In 2015–2016, Nusinow and colleagues identified a protein called PCH1 (Photoperiodic Control of Hypocotyl) that was repeatedly associated with the evening complex in AP-MS analysis of the plant circadian clock. They found that PCH1 is an essential structural component of phyB photobodies and that it stabilizes the active Pfr form of phyB by preventing its thermal reversion back to the inactive Pr state. This process allows phyB signaling to persist under changing light and temperature conditions. They focus on abscisic acid (ABA), a stress hormone sensed by chemical-induced dimerization (CID) modules made up of the PYR1 receptor and the phosphatase HAB1. They introduced mutations to engineer two new orthogonal CID modules, PYR1*MANDI/HAB1* and PYR1*AZIN/HAB1*, and a clear method for further module development. The new modules could be reprogrammed to be sensitive for varying ligands. Nusinow and his colleagues demonstrated in both Arabidopsis and Saccharomyces that the new modules could detect banned pesticides such as azinphos and create genetic circuits, an exciting discovery for plant synthetic biology.

Selected publications

In Vitro Transcription and Start Site Selection in Schizosaccharomyces pombe (2002) FKF1 and GIGANTEA Complex Formation is Required for Day-Length Measurement in Arabidopsis (2007) PCH1 Integrates Circadian and Light-Signaling Pathways to Control Photoperiod-Responsive Growth in Arabidopsis (2016) Identification of phospholipase Ds and phospholipid species involved in circadian clock alterations using CRISPR/Cas9-based multiplex editing of Arabidopsis (2024)