Meng-Qiu Dong, Ph.D.

Associate Investigator, TIMBR/NIBS, Beijing, China

Education

2001    Ph.D., Department of Molecular Biophysics & Biochemistry, Yale University, USA

1995    M.Sc., Shanghai Institute of Biochemistry, Chinese Academy of Sciences, China

1992    B.Sc., Department of Biology, Sichuan University, China

Experience

2007-    Associate Investigator, TIMBR/NIBS, Beijing, China

2003-2007    Postdoctoral Research Associate, The Scripps Research Institute, USA

2001-2003    Postdoctoral researcher, UCSD School of Medicine, USA

Research

Our lab is a place where biology intertwines with mass spectrometry.

On the biology side, our lab is interested in understanding the regulatory mechanisms of aging using C. elegans as a model. We quantify mRNA and protein abundance changes during the aging process of wild type and long-lived C. elegans mutants, and ask how they differ. We also analyze what happens to sub-cellular organelles such as mitochondria during aging. By cataloging such changes, we hope to describe the aging process in more detail, and lay the foundation for further investigations about the regulation of aging. At the center stage of our aging research is the Insulin/IGF-1 Signaling (IIS) pathway. Although it has been shown that components of the IIS pathway, from the insulin receptors to the FoxO transcription factors, all have important functions in lifespan regulation, the exact target genes downstream of FoxO that are responsible for the longevity of IIS mutants remain unclear. We are particularly interested in finding out those targets and then discerning the connections amongst them so that one can begin to understand the extraordinary effect of IIS on lifespan. We are also actively studying post-translational modifications (PTM) of DAF-16, which is the C. elegans FoxO. This key transcription factor is intricately regulated by a battery of kinases and a couple of phosphatases, including calcineurin, a calcium-and-calmodulin-dependent Ser/Thr phosphastase. The questions we are trying to address include how different environmental and internal cues (e.g. developmental stages) affect PTMs of DAF-16, and how the "modification code" of DAF-16 alters its transcriptional activity.

On the mass spectrometry (MS) front, our goal is to use and develop MS-based proteomic techniques to help answer biological questions. Besides protein identification, we routinely carry out quantitative proteomics analysis and PTM analysis of samples as complex as cell lysates. In collaboration with other researchers including the pFind group at the Institute of Computing Technology, we are currently developing methods to sequence peptides de novo (i.e. without searching a protein sequence database), to improve peptide identification from ETD spectra, and to probe protein-protein interactions by crosslinking followed by MS identification. The lab is equipped with four mass spectrometers, a Q Exactive, an LTQ-orbitrap with ETD, an ion trap instrument HCTultraPTM, and a triple-quadruple instrument TSQ Discovery.

Publications

1. Li WJ^†, Wang CW^†, Tao L^†, Yan YH^†, Zhang MJ, Liu ZX, Li YX, Zhao HQ, Li XM, He XD, Xue Y*,Dong MQ*. (2021) Insulin signaling regulates longevity through protein phosphorylation inCaenorhabditis elegans.Nat Commun. 12(1):4568.

2. Jones AX^†, Cao Y^†, Tang YL^†, Wang JH, Ding YH, Tan H, Chen ZL, Fang RQ, Yin J, Chen RC, Zhu X, She Y, Huang N, Shao F, Ye K, Sun RX, He SM, Lei X*,Dong MQ*. (2019) Improving mass spectrometry analysis of protein structures with arginine-selective chemical cross-linkers.Nat Commun. 10(1):3911.

3. Chen ZL^†, Meng JM^†, Cao Y^†, Yin JL, Fang RQ, Fan SB, Liu C, Zeng WF, Ding YH, Tan D, Wu L, Zhou WJ, Chi H, Sun RX,Dong MQ*, He SM*. (2019) A high-speed search engine pLink with systematic evaluation for proteome-scale identification of cross-linked peptides.Nat Commun. 10(1):3404.

4. Li ST^†, Zhao HQ^†, Zhang P^†, Liang CY, Zhang YP, Hsu AL,Dong MQ* (2019) DAF-16 stabilizes the aging transcriptome and is activated in mid-agedC. elegansto cope with internal stress.Aging Cell.2019 Feb 17:e12896.

5. Ding YH^†, Gong Z^†, Dong X^†, Liu K, Liu Z, Liu C, He SM,Dong MQ*, Tang C*. (2017) Modeling protein excited-state structures from "over-length" chemical cross-links.J Biol Chem.292(4):1187-1196.

6. Tan D^†, Li Q^†, Zhang MJ, Liu C, Ma C, Zhang P, Ding YH, Fan SB, Tao L, Yang B, Li X, Ma S, Liu J, Feng B, Liu X, Wang HW, He SM, Gao N, Ye K,Dong MQ*, Lei X*. (2016) Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states.eLife. 2016 Mar 8;5. pii: e12509.

7. Lu S^†, Fan SB^†, Yang B^†, Li YX, Meng JM, Wu L, Li P, Zhang K, Zhang MJ, Fu Y, Luo J, Sun RX, He SM*, andDong MQ*. (2015) Mapping Native Disulfide Bonds at a Proteome Scale.Nature Methods12(4):329-31.

8. Shen EZ^†, Song CQ^†, Lin Y^†, Zhang WH, Su PF, Liu WY, Zhang P, Xu J, Lin N, Zhan C, Wang X, Shyr Y, Cheng H*,Dong MQ* (2014) Mitoflash frequency in early adulthood predicts lifespan inCaenorhabditis elegans.Nature508(7494): 128-132.

9. Tao L, Xie Q, Ding YH, Li ST, Peng S, Zhang YP, Tan D, Yuan Z*,Dong MQ* (2013) CAMKII and Calcineurin Regulate the Lifespan ofCaenorhabditis elegansthrough the FOXO Transcription Factor DAF-16.eLife2:e00518.

10. Yang B^†, Wu YJ^†, Zhu M^†, Fan SB^†, Lin J, Zhang K, Li S, Chi H, Li YX, Chen HF, Luo SK, Ding YH, Wang LH, Hao Z, Xiu LY, Chen S, Ye K, He SM*, andDong MQ* (2012) Identification of Cross-linked Peptides from Complex Samples.Nature Methods9(9): 904-906.