Michaeleen Callahan-Doucleff, PhD

Nancy Nossal Postdoctoral Fellow
Laboratory of Chemical Physics - Clore Lab
NIDDK - National Institutes of Health
Bethesda, MD 20892
doucleffm {AT} niddk.nih.gov

Education | Publications | Research | Presentations | Muddy Shoe Reviews

Education:

University of California, Berkeley
Doctor of Philosophy in Chemistry - Biophysical Chemistry
University of California Graduate Fellowship
Advisor: David E. Wemmer
Collaborators: B. Tracy Nixon (Penn State); Sydney Kustu (UC Berkeley)
May 2007

University of California, Davis
Master of Science in Horticulture - Viticulture and Oenology
Advisor: Andrew Walker
August 2002

California Institute of Technology
Bachelor Science in Biology with Honors
Advisors: Frances Arnold and Mary Lidstrom
June 1998

Publications:

Click here for articles in PubMed.

Peer Reviewed Articles

Batchelor JD, Doucleff M, Lee CJ, Matsubara K, De Carlo S, Heideker J, Lamers MH, Pelton JG, Wemmer DE.
Structure and Regulatory Mechanism of Aquifex aeolicus NtrC4: Variability and Evolution in Bacterial Transcriptional Regulation.
J Mol Biol. 2008 in press. [PubMed]

Doucleff M, Clore GM.
Global jumping and domain-specific intersegment transfer between DNA cognate sites of the multi-domain transcription factor Oct-1.
Proc Natl Acad Sci. 2008 Sep 16;105(37):13871-6. [PubMed]

L Fawzi N, Phillips AH, Ruscio JZ, Doucleff M, Wemmer DE, Head-Gordon T.
Structure and Dynamics of the Abeta21-30 Peptide from the Interplay of NMR Experiments and Molecular Simulations
J Am Chem Soc. 2008 May 14;130(19):6145-58. [PubMed]

Doucleff M, Pelton JG, Lee PS, Nixon BT, Wemmer DE.
Structural basis of DNA recognition by the alternative sigma-factor, sigma54.
J Mol Biol. 2007 Jun 15;369(4):1070-8. [PubMed] on the cover

Chen B, Doucleff M, Wemmer DE, De Carlo S, Huang HH, Nogales E, Hoover TR, Kondrashkina E, Guo L, Nixon BT.
ATP ground- and transition states of bacterial enhancer binding AAA+ ATPases support complex formation with their target protein, sigma54.
Structure. 2007 Apr;15(4):429-40.[PubMed]

Draper O, Middleton R, Doucleff M, Zambryski PC.
Topology of the VirB4 C terminus in the Agrobacterium tumefaciens VirB/D4 type IV secretion system.
J Biol Chem. 2006 Dec 8;281(49):37628-35. [PubMed]

Nixon BT, Yennawar HP, Doucleff M, Pelton JG, Wemmer DE, Krueger S, Kondrashkina E.
SAS solution structures of the apo and Mg2+/BeF3(-)-bound receiver domain of DctD from Sinorhizobium meliloti.
Biochemistry. 2005 Oct 25;44(42):13962-9.[PubMed]

Doucleff M, Malak LT, Pelton JG, Wemmer DE.
The C-terminal RpoN domain of sigma54 forms an unpredicted helix-turn-helix motif similar to domains of sigma70.
J Biol Chem. 2005 Dec 16;280(50):41530-6.[PubMed]

Doucleff M, Chen B, Maris AE, Wemmer DE, Kondrashkina E, Nixon BT.
Negative regulation of AAA + ATPase assembly by two component receiver domains: a transcription activation mechanism that is conserved in mesophilic and extremely hyperthermophilic bacteria.
J Mol Biol. 2005 Oct 21;353(2):242-55.[PubMed]

Lowery TJ, Doucleff M, Ruiz EJ, Rubin SM, Pines A, Wemmer DE.
Distinguishing multiple chemotaxis Y protein conformations with laser-polarized 129Xe NMR.
Protein Sci. 2005 Apr;14(4):848-55. [PubMed]

Doucleff M, Jin Y, Gao F, Riaz S, Krivanek AF, Walker MA.
A genetic linkage map of grape, utilizing Vitis rupestris and Vitis arizonica.
Theor Appl Genet. 2004 Oct;109(6):1178-87. [PubMed]

Research:

1. Kinetics and Dynamics of DNA Binding Proteins
(Postdoctoral Research)
Coming soon...

2. Activation by Phosphorylation
(Graduate Resarch)

Bacteria sense and respond to their environment using a signal protein, called a response regulator. When sensors on the cell's surface bind to important compounds outside the cell, the sensors activate the response regulator by adding a phosphate molecule to its protein surface. Once phosphorylated, the response regulator can 'turn-on' genes needed to respond to changes in the cell's environment.
The first part of my graduate research focused on understanding the mechanism of 'activation via phosphorylation' - a process fundamental to all kingdoms of life.
By combining biochemical and structural techniques, we showed that phoshporylation of the response regulator causes a drastic change in its dimer conformation. In the unphosphorylated state the response regulator forms a dimer that locks an attached ATPase domain in an inactive configuration. Phosphorylation stablizes an alternate dimer where the ATPase domain is 'free' to form an active oligomer. With a fully functioning ATPase, the response regulator can start 'turning-on' genes required to respond to the environmental signal.
Sequence and structural analyses predict that this mechanism of activation may be general to many types of response regulators across the bacterial kingdom.

3. High-resolution Structures of Bacterial Transcription Factor Sigma-54
(Graduate Research)

Presentations:

Invited Talks

FASEB Conference on "Mechanisms & Regulation of Prokaryotic Transcription," Saxtons River, Vermont, June 2007

Muddy Shoe Reviews:

I am a regular contributor to the "Muddy Shoe Review" in the Washington Running Report , a magazine covering running and racing in the Washington-Baltimore area. It is published bi-monthly and available at local sports stores and by subscription . Check out my trail reviews:

Mountain High: Three Challenging Climbs Close to D.C.