Celia W. Goulding

Professor, Molecular Biology and Biochemistry

Professor, Pharmaceutical Sciences

B.S., Kings College, London, UK, Chemistry & Mathematics

Ph.D., Kings College, London, UK, Physical Organic Chemistry

Postdoctoral Researcher, University of Michigan, Biochemistry (Matthews' lab)

Research Faculty, UCLA, TB Structural Genomics (Eisenberg lab)

Phone: (949) 824-0337
Fax: (949) 824-8551
Email: celia.goulding@uci.edu

University of California, Irvine
2212 Natural Sciences 1
Mail Code: 3900
Irvine, CA 92697

picture of Celia W. Goulding

structural biology, biochemistry, proteomics, microbiology, X-ray crystallography
URL LabWebsite
The principal focus of my lab is to utilize proteomic and crystallographic techniques to elucidate and characterize new systems of protein complexes in Mycobacterium tuberculosis. Our overall goal is to create a systems approach to shift the focus of structural biology from a single protein to molecular assemblies. The systems of immediate interest contain potential anti-TB protein drug targets and protein membrane components. We also are studying contact-dependent growth inhibition in gram-negative bacteria.

Novel Mycobacterial Heme Uptake System

Iron is an essential metal for life. Mycobacteria must import iron from its host. Molecules involved in iron chelating pathways are well characterized, such as those involving exochelins and siderophores. Recently, it has been shown that during the early stages of S. aureus infection the major source of nutrient iron is heme rather than transferrin iron. A potential mycobacterial secreted hemophore (heme scavenging protein) has been identified in mycobacteria. Also, a potential cytosolic heme-degrading protein has been identified. Hence, a novel mcobacterial heme uptake system may exisit. My laboratory will be dissecting this pathway both structrually and biochemically. Thus far, the X-ray crystal structure of the potential hemophore has been deteremined, and a potential heme uptake membrane protein has been identified by mass spectrometry. Investigation into this uptake system is on-going.

Disulfide Bond Isomerase System

Disulfide bond-forming (Dsb) proteins have been shown to be involved in virulence in many pathogenic bacteria. They are oxidoreductase proteins that have a variety of functions including chaperone activity, electron transfer and disulfide bond isomerase activity. It has been predicted that of the 161 potential secreted proteins of M. tuberculosis approximately 60 % of these contain at least one disulfide bon. Hence, Dsb proteins which assist in folding secreted proteins into their correct conformation and assist in disulfide bond formation are of great importance for the survival of M. tuberculosis. Utilizing bioinformatics, two secreted Dsb proteins have been identified in M. tuberculosis, one of which is my target protein to investigate the secreted disulfide bond isomerase system of mycobacteria. The secreted proteins which these two Dsb proteins interact with is presently under investigation.

Contact-dependent Growth Inhibition

Contact-dependent growth inhibition is a newly discovered mechanism of bacterial communication and competition. CDI toxin and immunity proteins are found in a variety of gram-negative bacteria, and are highly sequence-divergent across species. Some toxins within the CDI system require activation by forming a protein complex with a target cell protein – termed a “permissive” factor – adding a new level of complexity to the CDI system. In collaboration with the Hayes and Low labs at UCSB and MCSG, we plan
1) To solve toxin/immunity complexes that are sequence-divergent in collaboration with MCSG, in order to shed light on the requirements for toxin neutralization. Additionally, we will characterize the function of each toxin. Thus far, MCSG has cloned six toxin/immunity pairs and have two diffracting crystals, one toxin/immunity complex and one immunity protein alone. UCSB has also received these clones to biochemically characterize them.
2) To develop a screen to identify ‘permissive’ factors and biochemically characterize them. UCSB has developed a 96-well plate GFP-based assay to rapidly identify such factors.
3) To structurally characterize the protein complexes in the presence of "permissive" factors. UCI has solved the structure of a UPEC539 toxin in complex with its permissive factor CysK, which has informed functional studies.
Publications The Structure and Interactions of Periplasmic Domains of Crucial MmpL Membrane Proteins from Mycobacterium tuberculosis.
Chim N, Torres R, Liu Y, Capri J, Batot G, Whitelegge JP, Goulding CW.
Chem Biol. 2015 Aug 20;22(8):1098-107
  Contact-dependent growth inhibition (CDI) and CdiB/CdiA two-partner secretion proteins.
Willett JL, Ruhe ZC, Goulding CW, Low DA, Hayes CS.
J Mol Biol. 2015 Sep 17. pii: S0022-2836(15)00521-5.
  Fe(2+) substrate transport through ferritin protein cage ion channels influences enzyme activity and biomineralization.
Behera RK, Torres R, Tosha T, Bradley JM, Goulding CW, Theil EC.
J Biol Inorg Chem. 2015 Sep;20(6):957-69
  The structure of a contact-dependent growth-inhibition (CDI) immunity protein from Neisseria meningitidis MC58.
Tan K, Johnson PM, Stols L, Boubion B, Eschenfeldt W, Babnigg G, Hayes CS, Joachimiak A & Goulding CW.
Acta Crystallogr F Struct Biol Commun. 2015 Jun 1;71(Pt 6):702-709.
  Characterization of a Mycobacterium tuberculosis nanocompartment and its potential cargo proteins.
Contreras H, Joens MS, McMath LM, Le VP, Tullius MV, Kimmey JM, Bionghi N, Horwitz MA, Fitzpatrick JA, Goulding CW.
J Biol Chem. 2014 Jun 27;289(26):18279-8
  Crystallographic and spectroscopic insights into heme degradation by Mycobacterium tuberculosis MhuD.
Graves AB, Morse RP, Chao A, Iniguez A, Goulding CW, Liptak MD.
Inorg Chem. 2014 Jun 16;53(12):5931-40
  Heme uptake in bacterial pathogens.
Contreras H, Chim N, Credali A, Goulding CW.
Curr Opin Chem Biol. 2014 Apr;19:34-41.
  Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase.
Torres R, Lan B, Latif Y, Chim N, Goulding CW.
Acta Crystallogr D Biol Crystallogr. 2014 Apr;70(Pt 4):1074-85.
  CdiA from Enterobacter cloacae delivers a toxic ribosomal RNase into target bacteria.
Beck CM, Morse RP, Cunningham DA, Iniguez A, Low DA, Goulding CW, Hayes CS.
Structure. 2014 May 6;22(5):707-18
  Insights into redox sensing metalloproteins in Mycobacterium tuberculosis.
Chim N, Johnson PM, Goulding CW.
J Inorg Biochem. 2014 Apr;133:118-26.
  Structural and biochemical characterization of the essential DsbA-like disulfide bond forming protein from Mycobacterium tuberculosis.
Chim N, Harmston CA, Guzman DJ, Goulding CW.
BMC Struct Biol. 2013 Oct 18;13:23.
  The Mycobacterial tuberculosis Secreted Protein, Rv0203 Transfers Heme to Membrane Proteins MmpL3 and MmpL11
Owens CP, Chim N, Harmston CA, Contreras H, Iniguez A, and Goulding CW
J. Biol. Chem, 2013, 288(30); 21714-28.
  Structures of Oligomers of a Peptide from ß-Amyloid
Pharm JD, Chim N, Goulding CW and Nowick JS
J Am Chem Soc. 2013 Aug 21;135(33):12460-7
  A new way to degrade heme: the Mycobacterium tuberculosis enzyme MhuD catalyzes heme degradation without generating CO.
Nambu S, Matsui T, Goulding CW, Takahashi S, Ikeda-Saito M.
J. Biol. Chem, 2013, 288(14); 10101-9.
  S. aureus IsdG and IsdI degrades heme with liberating formaldehyde
Matsui T, Nambu S, Ono Y, Goulding CW, Tsumoto K, Ikeda-Saito M.
Biochemistry 2013, 52(18); 3025-7.
  Insights on how the Mycobacterium tuberculosis heme uptake pathway can be used as a drug target
Owens CP, Chim N, and Goulding CW
Future Medicinal Chemistry, 2013, 5(12); 1391-403
  The structural characterization of bacterioferritin, BfrA, from Mycobacterium tuberculosis
McMath LM, Contreras H, Owens CP and Goulding, CW
J. of Porphyrins and Phthalocyanine, 2013, 17 (3); 229-239.
  Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems
R. Morse, KC Nikolakakis, JLE Willett, E Gerrick, DA Low, CS Hayes & Celia W. Goulding
Proc Natl Acad. Sci, 2012, 109(25):21480-5.
  Structural insights into RipC, a putative citrate lyase ß subunit from a Yersinia pestis virulence operon.
Torres R, Chim N, Sankaran B, Pujol C, Bliska JB, Goulding CW.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Jan 1;68(Pt 1):2-7. Epub 2011 Dec 24.
  The Near-Iron Transporter (NEAT) Domains of the Anthrax Hemophore IsdX2 Require a Critical Glutamine to Extract Heme from Methemoglobin.
Honsa E, Owens CP, Goulding CW and Maresso AW
J. Biol. Chem, 2013, 288(12); 8479-90.
  Advances in Mycobacterium tuberculosis Therapeutic Discovery Utilizing Structural Biology
N. Chim, C.P. Owens, H. Contreras & C. W. Goulding
Infectious Disorders – Drug Targets, 2012, Nov 16, epub
  Plasma antibody profiles as diagnostic biomarkers for tuberculosis.
Khan IH, Ravindran R, Krishnan VV, Awan IN, Rizvi SK, Saqib MA, Shahzad MI, Tahseen S, Ireton G, Goulding CW, Felgner P, DeRiemer K, Khanum A, Luciw PA.
Clin Vaccine Immunol. 2011 Dec;18(12):2148-53. Epub 2011 Oct 5.
  Biochemical, structural and molecular dynamics analyses of the potential virulence factor RipA from Yersinia pestis.
Torres R, Swift RV, Chim N, Wheatley N, Lan B, Atwood BR, Pujol C, Sankaran B, Bliska JB, Amaro RE, Goulding CW.
PLoS One. 2011;6(9):e25084. Epub 2011 Sep 26.
  The TB Structural Genomics Consortium: A decade of progress. Chim N, Habel JE, Johnston JM, Krieger I, Miallau L, Sankaranarayanan R, Morse RP, Bruning J, Swanson S, Kim H, Kim CY, Li H, Bulloch EM, Payne RJ, Manos-Turvey A, Hung LW, Baker EN, Lott JS, James MN, Terwilliger TC, Eisenberg DS, Sacchettini JC, Goulding CW.
Tuberculosis (Edinb). 2011 91(2):155-72
  Characterization of heme ligation modes of Rv0203, a secreted heme-binding protein involved in Mycobacterium tuberculosis heme uptake.
Owens CP, Du J. Dawson JD and Goulding CW.
Biochemistry, 2012, 51 (7), 1518-31
  Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore
Ekworomadu MC, Poor CB, Owens CP, Murphy F, Balkabasi E, Honsa, E, He C, Goulding CW and Maresso AW
PLoS Pathogens, 2012, Mar 8(3);e1002559, 1-16.
  Discovery and characterization of a unique mycobacterial heme acquisition system.
Tullius MV, Harmston CA, Owens CP, Chim N, Morse RP, McMath LM, Iniguez A, Kimmey JM, Sawaya MR, Whitelegge JP, Horwitz MA, Goulding CW.
Proc Natl Acad Sci U S A. 2011, 108(12):5051-6.
  Crystallization and preliminary X-ray crystallographic analysis of a Mycobacterium tuberculosis ferritin homolog, BfrB.
McMath LM, Habel JE, Sankaran B, Yu M, Hung LW, Goulding CW.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 66(12):1657-61.
  An extracellular disulfide bond forming protein (DsbF) from Mycobacterium tuberculosis: Structural, biochemical and gene expression analysis,
Chim N, Riley R, The J, Im S, Segelke B, Lekin T, Yu M, Hung L-W,Terwilliger T, Whitelegge JP and Goulding CW,
J. Mol. Biol, 2010, 365(3): 1211-26
  Unusual Diheme Conformation of the Heme-Degrading Protein from Mycobacterium tuberculosis,
Chim N, Iniguez A, Nguyen TQ, Goulding CW,
J Mol Biol, 2010, 396(5), 595-608
  Advances in Mycobacterium tuberculosis structural genomics: investigating potential chinks inthe armor of a deadly pathogen.
N. Chim, L.M. McMath, M. Beeby and C.W. Goulding
Infectious Disorders – Drug Targets, 2009, 9, 475-92.
  Profiling Antibodies to Mycobacterium tuberculosis (M. tb.) by Multiplex Microbead Suspension Arrays for Serodiagnosis of TB.
I. H. Khan, R. Raindran, J. Yee, M. Ziman, D.M. Lewisohn, M.L. Gennaro, J.L. Fylnn, C.W. Goulding, K. Deriemer, N.W. Lerche and P.A. Luciw,
Clin Vaccine Immunol, 2008, 15, 433-8.
  Structural genomics: from genes to structures with valuable materials and many questions in between.
B.G. Fox, C Goulding, M.G. Malkowski, L. Stewart and A. Deacon.
Nature Methods, 2008, 52: 129-32.
Graduate Programs Structural Biology and Molecular Biophysics

Cellular and Molecular Biosciences

Medicinal Chemistry and Pharmacology

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Last updated 09/30/2015