Research Supplement to Promote Diversity in Health-Related Research

促进健康相关研究多样性的研究补充

• 批准号: 10814602
• 负责人: Carrie L Partch
• 金额: $ 14.78万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10814602
• 关键词: Architecture; Behavior; Binding Sites; Biochemical; Biochemistry; Biological; Biological Clocks; Cellular biology; Circadian Rhythms; Clock protein; Complex; Cues; Cyanobacterium; Funding; Genetic; Health; Hour; Human; Intervention; Light; Link; Mammals; Molecular; National Institute of General Medical Sciences; Physiology; Post-Translational Protein Processing; Protein Dynamics; Proteins; Research; Resources; Signal Transduction; System; Time; biophysical techniques; circadian; comparative; enzyme activity; flexibility; pharmacologic; programs; protein function; structural biology

Abstract of the Funded Project (R35 GM141849) Circadian rhythms arise from genetically encoded clocks that are intimately linked to external cues like light to synchronize physiology and behavior with the 24-hour solar cycle. Although the genetic networks that give rise to circadian rhythms are now relatively well established, we still don’t understand many of the fundamental, molecular steps that determine the ~24-hour basis of these clocks and how they respond to external time-setting cues. By integrating structural biology and solution biophysical methods with biochemistry and cell biology, we aim to determine the underlying biochemical principles that lead to the day-long timescale of circadian signaling and uncover the mechanisms that allow biological clocks to faithfully maintain intrinsic timing and respond robustly to external cues. With prior NIGMS funding, we studied clock systems from mammals and cyanobacteria to discover how different clock proteins assemble into regulatory complexes and identified how protein dynamics, enzyme activity and/or post-translational modifications impact clock timing. Our comparative biochemical approach highlighted surprising commonalities, such as the competition for mutually exclusive binding sites, between these clocks despite their different molecular architectures. Here, we will continue to pursue the structural basis of protein assemblies from diverse biological clocks, determine the consequences of post- translational modifications on clock protein function, study the molecular basis for entrainment of clocks to external cues, and seek out new inroads for pharmacological intervention. Funding from the MIRA program would provide us with the resources and flexibility to explore commonalities in mechanisms of biological timekeeping across a diverse array of species from cyanobacteria to humans.

资助项目（R35 GM141849）摘要

项目成果

Meet the authors: Jonathan Philpott and Carrie L. Partch.

认识一下作者：乔纳森·菲尔波特和凯莉·L·帕奇。

• DOI: 10.1016/j.molcel.2023.04.016
• 发表时间: 2023
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Philpott,JonathanM;Partch,CarrieL
• 通讯作者: Partch,CarrieL

Cryptochrome proteins regulate the circadian intracellular behavior and localization of PER2 in mouse suprachiasmatic nucleus neurons.

• DOI: 10.1073/pnas.2113845119
• 发表时间: 2022-01-25
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Smyllie NJ;Bagnall J;Koch AA;Niranjan D;Polidarova L;Chesham JE;Chin JW;Partch CL;Loudon ASI;Hastings MH
• 通讯作者: Hastings MH

PAS dimerization at the nexus of the mammalian circadian clock.

• DOI: 10.1016/j.jmb.2023.168341
• 发表时间: 2023-11
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Diksha Sharma;C. Partch

Quantification of protein abundance and interaction defines a mechanism for operation of the circadian clock.

• DOI: 10.7554/elife.73976
• 发表时间: 2022-03-14
• 期刊: eLife
• 影响因子: 7.7
• 作者: Koch AA;Bagnall JS;Smyllie NJ;Begley N;Adamson AD;Fribourgh JL;Spiller DG;Meng QJ;Partch CL;Strimmer K;House TA;Hastings MH;Loudon ASI
• 通讯作者: Loudon ASI