EDUCATION:

CONTACT INFORMATION:

Email dharlow@lbl.gov
Phone 510-495-2620
Office 4550
Bench 39
Address

Current Research

Nearly all efforts to engineer biology, including biomanufacturing of chemicals using fermentation, production of new vaccines or biological therapeutics, gene editing/gene therapy, and most biological experiments in general require the construction of 1-20 kilobase DNA molecules with a desired sequence. Today, most DNA constructs are created by amplifying, modifying, and combining existing template sequences using “molecular cloning” techniques that are time intensive and often fail for poorly understood reasons, resulting in lost time and missed research opportunities. We are developing new tools for rapid synthesis of multi-kilobase DNA that we hope will dramatically accelerate the “design-build-test-learn” cycle in bioengineering and ultimately bring about a new era of genome-scale synthetic biology.

Publications

  • Dror RO, Mildorf TJ, Hilger D, Manglik A, Borhani DW, Arlow DH, Philippsen A, Villanueva N, Yang Z, Lerch MT, Hubbell WL, Kobilka BK, Sunahara RK, Shaw DE. Structural basis for nucleotide exchange in heterotrimeric G proteins. Science. 2015 Jun 19;348(6241):1361-5.
    PubMed PMID: 26089515.
  • Dror RO, Green HF, Valant C, Borhani DW, Valcourt JR, Pan AC, Arlow DH, Canals M, Lane JR, Rahmani R, Baell JB, Sexton PM, Christopoulos A, Shaw DE. Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs. Nature. 2013 Nov 14;503(7475):295-9.
  • Nygaard R, Zou Y, Dror RO, Mildorf TJ, Arlow DH, Manglik A, Pan AC, Liu CW, Fung JJ, Bokoch MP, Thian FS, Kobilka TS, Shaw DE, Mueller L, Prosser RS, Kobilka BK. The Dynamic Process of β2-Adrenergic Receptor Activation. Cell. 2013 Jan 31;152(3):532-42.
  • Cheng Z, Srinivasan Y, Arlow DH, Fung JJ, Palmer D, Zheng Y, Green HF, Pandey A, Dror RO, Shaw DE, Weis WI, 5, Coughlin SR, Kobilka BK. High-resolution crystal structure of human Protease-Activated Receptor 1 bound to the antagonist vorapaxar. Nature. 2012 Dec 20;492(7429):387-92.
  • Kruse AC, Hu J, Pan AC, Arlow DH, Rosenbaum DM, Rosemond E, Green HF, Liu T, Chae PS, Dror RO, Shaw DE, Weis WI, Wess J, Kobilka BK. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature. 2012 Feb 22;482(7386):552-6.
  • Dror RO, Arlow DH, Maragakis P, Mildorf TJ, Pan AC, Xu H, Borhani DW, Shaw DE. Activation mechanism of the β2-adrenergic receptor. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18684-18689.
  • Dror RO, Pan AC, Arlow DH, Borhani DW, Maragakis P, Shan Y, Xu H, Shaw DE. Pathway and mechanism of drug binding to G-protein-coupled receptors. Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13118-23.
  • Dror RO, Pan AC, Arlow DH, Shaw DE. Probing the Conformational Dynamics of GPCRs with Molecular Dynamics Simulation (book chapter). 2011. G protein-coupled receptors: from structure to function. Cambridge: RSC Pub. ISBN: 978-1-84973-183-6.
  • Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, Rasmussen SG, Choi HJ, Devree BT, Sunahara RK, Chae PS, Gellman SH, Dror RO, Shaw DE, Weis WI, Caffrey M, Gmeiner P, Kobilka BK. Structure and function of an irreversible agonist-β(2) adrenoceptor complex. Nature. 2011 Jan 13;469(7329):236-40.
  • Charest-Marcotte A, Dufour CR, Wilson BJ, Tremblay AM, Eichner LJ, Arlow DH, Mootha VK, Giguère V. The homeobox protein Prox1 is a negative modulator of ERRα/PGC-1α bioenergetic functions. Genes Dev. 2010 Mar 15;24(6):537-42.
  • Baughman JM, Nilsson R, Gohil VM, Arlow DH, Gauhar Z, Mootha VK. A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. PLoS Genet. 2009 Aug;5(8):e1000590.
  • Dror RO, Arlow DH, Borhani DW, Jensen MØ, Piana S, Shaw DE. Identification of two distinct inactive conformations of the β2-adrenergic receptor reconciles structural and biochemical observations. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4689-94.
  • Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007 Nov 29;450(7170):736-40.
  • Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM. Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6570-5.

Awards

NSF Graduate Research Fellowship (2012)