Proteins in a cell are metastable and not only threatened by the crowded cellular environment, but also affected by mutations, mistakes in translation and posttranslational modifications, and unpredictable environmental stresses. Proteins tend to misfold with age, which impairs protein homeostasis and is believed to be an underlying cause for many age-related diseases, including Alzheimer’s and Parkinson’s. Protein homeostasis (proteostasis), maintained through balancing protein folding and misfolding, is the key for biological systems to live long and prosper, as almost all cellular functions are fulfilled by specific proteins.
The Zhou lab studies mechanisms underlying the cellular aging process, with a particular emphasis on proteostasis. We study protein folding and misfolding in both young and aging cells, with the goal of understanding the events that lead to the loss of proteostasis during cellular aging and disease as well as identifying mechanisms that can be exploited to rejuvenate aging cells. Our lab uses the budding yeast Saccharomyces cerevisiae to study these topics systematically and comprehensively at the molecular and cellular levels. Budding yeast has been proven to be a great model system for research on cellular aging and revealed longevity mechanisms that are highly conserved in metazoan. By leveraging genetic tools and libraries, we hope to progress quickly on projects to provide insights for fundamental biological questions. We are also developing new methodologies and platforms to broaden our technology portfolio that can be unleashed to break through current limitations in the field and improve our understanding of aging and age-related diseases.
Why it matters
Aging is a general physiological deterioration that constitutes the primary risk factor for major human pathologies, including cancer, cardiovascular diseases, and neurodegenerative diseases. Research to develop cures for these diseases has been hampered because we lack a clear understanding of the factors that underlie the aging process. Elucidating these factors remains an important frontier in aging research and will accelerate our ability to intervene in age-related disease. Recent setbacks in clinical trials for Alzheimer’s disease have sparked a new wave of basic research to understand protein folding and misfolding during aging and disease progression. Proteostasis is the basis for all cellular functions, and its mechanisms are highly conserved. Yeast has long served as a living test tube for proteostasis research and will continue to be a centerpiece of our further understanding of proteostasis in both healthy young individuals and older adults manifesting age-related diseases.
Proteins are the building blocks of life. My lab focuses on understanding age-related protein folding and disease-related misfolding as an essential component of efforts to intervene in age-related disease.
Kai Zhou, PhD
Dr. Zhou, the first Buck Fellow, joined the Institute directly after his thesis work. Dr. Zhou received his PhD in molecular and integrative physiology from the University of Kansas School of Medicine and the Stowers Institute for Medical Research.
Dr. Zhou has been awarded a prestigious $2.4 million Early Independence Award from the National Institutes of Health. As part of the NIH Director’s Award in the High-Risk, High-Reward Research program, this five-year grant allows Dr. Zhou to skip traditional postdoctoral training and move immediately into independent research.
Catherine Chang Dominican University Master's Student
Catherine Chang received her bachelor's degree in Biochemistry and Molecular Biology from UC Santa Cruz in 2016. As an undergraduate student, she investigated the effects of macromolecular crowding on protein folding. Catherine joined the Zhou Lab in August 2018 where she continues to pursue her research interest of protein folding and regulation. When away from the lab, you can expect to find Catherine enjoying the great outdoors!
Matt Domnauer PhD Candidate, Buck-USC Biology of Aging Program
Matt Domnauer is studying the biology of aging through a joint PhD program between the Buck Institute and the University of Southern California. He graduated from UC Santa Cruz in 2016 with a degree in Molecular, Cell, and Developmental biology where he studied the biochemical mechanisms regulating cell size and growth rate. Matt joined the Zhou lab in 2018 where he studies how cellular stress affects protein homeostasis in aging cells.
Qingqing Liu, PhD Postdoctoral Research Fellow
Dr. Liu is from China and holds a bachelor’s degree in biological engineering. In 2017, she earned her PhD in microbiology and immunology at the China Agricultural University, where she worked on the circadian clock and the ubiquitin-proteasome system. Interested in protein homeostasis and aging, she joined the Zhou lab in February 2018. She is optimistic and believes that she will overcome all kinds of difficulties with her perseverance. In her spare time, she enjoys doing traditional Chinese needlework, which makes her relaxed and happy.
- He, C., Zhou, C., Kennedy, B. K. (2018 Mar 8). The yeast replicative aging model. Biochim Biophys Acta. (Epub ahead of print)
- Ruan, L.*, Zhou, C.*, et al. (2017). Cytosolic proteostasis via importing of misfolded proteins into mitochondria. Nature, 543(7645), 443–446. (*Equal contribution)
- Zhou, C., et al. (2014). Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells. Cell, 159, 530–542. PMID: 25417105.
- Zhou, C., et al. (2014). Life history: Mother-specific proteins that promote aging. Biol, 24, 24, R1162-4.
- Zhou, C., et al. (2011). Motility and segregation of hsp104-associated protein aggregates in budding yeast. Cell, 147, 1186–1196.