Carrie L. Partch
Carrie L. Partch | |
---|---|
Born | Carrie L. Stentz 30 November 1973 Kirkland, Washington, USA |
Alma mater | |
Scientific career | |
Fields | Oregon Health Sciences University
University of Texas Southwestern
University of California, Santa Cruz |
Thesis | Signal transduction mechanisms of cryptochrome (2006) |
Doctoral advisor | Aziz Sancar |
Website | https://www.partchlab.com/ |
Carrie L. Partch (born 30 November 1973) is an
Academic career
In her undergraduate career at the
In her post-doctoral research, Partch focused on the interaction of the
Partch began her career in teaching as an assistant professor (2011-2017) at UC Santa Cruz in the Department of Chemistry and Biochemistry. Partch went on to become an associate professor (2017-2019), and is now a professor (2019–present) in UC Santa Cruz's Chemistry and Biochemistry Department.[3]
Early research
Early research at Oregon Health Sciences University
Partch’s early research at Oregon Health Sciences University has a broad biochemical scope, her first publication focusing on the regulation of IL-15-stimulated TNF-alpha production, a study applicable to patients with rheumatoid arthritis.[9] Similarly, Partch’s second publication on sperm-specific proteins which interact with A-kinase anchoring proteins[10] showcases fascinating biochemical research not yet involving chronobiology.
PhD Thesis Research at UNC Chapel Hill
Following Partch's earliest research at OHSU, she began to home in on cryptochrome proteins and their signal transduction mechanisms, the focus of her PhD thesis.[11] In her thesis, Partch discusses convergence in plant and animal cryptochromes, translational repressors in biological clock feedback loops, and most notably, incorporates extensive research of biological clocks into her dissertation. Partch studied mammalian cryptochromes’ interactions with protein phosphatase 5 to investigate how inhibition of PP5 affects the activity of casein kinase I epsilon, the major clock kinase. Partch delves further into her passion for chronobiology in her thesis.
Current research
Partch's Lab currently focuses on the proteins known to circadian timekeeping, and utilizes a range of structural and biophysical techniques in order to characterize the biological role of these proteins including NMR spectroscopy and X-ray crystallography.[3] Current projects include both mammalian and cyanobacterial timekeeping mechanisms. Notably, the lab recently published work in the journal Science, elucidating the role of the protein SasA in the cooperative binding of KaiB to the KaiC hexamer in the cyanobacterial circadian clock.[12] In 2020, the lab published a paper describing how the mammalian circadian protein PERIOD and its cognate kinase Casein Kinase 1 form a molecular switch to regulate PERIOD protein stability, and therefore circadian periodicity.[13]
Role of SasA protein in cyanobacteria
Previously, many models of cyanobacterial time keeping were based solely on the continuous phosphorylation of the Kai proteins (KaiA, KaiB, and KaiC) with SasA and CikA providing only input-output signaling. These earlier dependent models relied solely on KaiC acting as the main component of the circadian oscillator with KaiA being used to phosphorylase Threonine and Serine and KaiB being used for their subsequent dephosphorylation.[14] For these reactions to work, ATP is broken down to ADP to provide the necessary energy and phosphate groups necessary to power these reactions. Partch challenged this assumption by modeling the effect of SasA proteins in differing concentrations of KaiA, KaiB, and KaiC. It was found that SasA uses structural mimicry to help fold-switched KaiB bind to the KaiC hexamer so that the nighttime repressive complex can be formed.[15] This maintains the rhythmicity of the circadian oscillator during limiting concentrations of KaiB by allowing both of the hexamers to auto phosphorylate and dephosphorylate threonine and serine. Conversely, SasA proteins compete with KaiB proteins for the binding of the KaiC hexamer when the concentration of SasA exceeds that of KaiB. The competition between these proteins can be mitigated when the concentration of SasA is less than or equal to half of the concentration of KaiB. Lower concentrations of SasA allow for KaiB to bind to the KaiC hexamer solely; it does not need to compete for KaiC binding spots with SasA.
PERIOD proteins and CK1
Carrie Partch has made significant discoveries pertaining to PERIOD protein's role in regulating the circadian clock. PERIOD proteins,
Phosphoswitch Model
Previous research has been completed to identify key components of Familial Advanced Sleep Phase Syndrome (FASPS) also known as Advanced sleep phase disorder.[18][19] However, Partch contributed to the development of the formalized phosphoswitch model, compiling the previous research into a single model. The phosphoswitch model is a proposed regulatory mechanism for the stabilization and destabilization of the PERIOD protein in the mammalian circadian clock. This model explains the circadian sensitivity and phenotypic differences caused by mutations within the PER2 protein at site 662 and site 478. A downstream mutation from a serine to a glycine at site 662 leads to a shorter period, underphosphorylation, and PER2 destabilization. Because of the resulting shorter period, the phosphoswitch model is a possible mechanism for Familial Advanced Sleep Phase Syndrome (FASPS). The exact role of phosphorylation within the FASP region in the stabilization of PER2 is not yet known.[20]
Awards
- 2018 - “Aschoff’s Rule”, Gordon Conference on Chronobiology[21]
- 2018 - Margaret Oakley Dayhoff Award, Biophysical Society
- 2022 - NAS Award in Molecular Biology
References
- ^ "UCSC Campus Directory". Archived from the original on 11 May 2021.
- ^ "Carrie Partch". scholar.google.com. Retrieved 11 December 2021.
- ^ a b c d "Partch Lab Website". Archived from the original on 12 July 2016.
- PMID 15751956.
- PMID 16790549.
- PMID 19324882.
- PMID 21512126.
- PMID 22653727.
- PMID 10453029. Retrieved 10 April 2023 – via PubMed.
- ^ PMID 11278869.
- ^ Partch, Carrie (2006). "Signal Transduction Mechanisms of Cryptochrome".
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(help) - S2CID 238475334.
- license.
- ^ Snijder, J., Axmann, I.M. (2019). The Kai-Protein Clock—Keeping Track of Cyanobacteria’s Daily Life. In: Harris, J., Marles-Wright, J. (eds) Macromolecular Protein Complexes II: Structure and Function . Subcellular Biochemistry, vol 93. Springer, Cham. https://doi.org/10.1007/978-3-030-28151-9_12
- ^ Chavan AG, Swan JA, Heisler J, Sancar C, Ernst DC, Fang M, Palacios JG, Spangler RK, Bagshaw CR, Tripathi S, Crosby P, Golden SS, Partch CL, LiWang A. Reconstitution of an intact clock reveals mechanisms of circadian timekeeping. Science. 2021 Oct 8;374(6564):eabd4453. doi: 10.1126/science.abd4453. Epub 2021 Oct 8. PMID 34618577; PMCID: PMC8686788.
- PMID 28886335.
- . Retrieved 27 April 2023.
- S2CID 1848310.
- PMID 17218255.
- PMID 33933351.
- ^ "Prize Winners of Aschoff's Rule". www.clocktool.org. Archived from the original on 9 August 2020.