Bio

Honors & Awards


  • Jane Coffin Childs Postdoctoral Fellowship, Jane Coffin Childs Memorial Fund for Medical Research (2011-2014)
  • Distinguished Dissertation Award Finalist, Council of Graduate Schools/Proquest (2011)
  • Charles T. Lester Award, Emory University (2010)
  • ARCS Scholar Fellowship, Achievment Rewards for College Scientists (ARCS) Foundation (2008-2009)
  • ORDER (On Recent Discoveries of Emory Researchers) Teaching Scholar, Emory University (2007)
  • MSA Presidential Student Award, Microscopy Society of America (MSA) (2008)
  • Osbourne R. Quayle Fellowship, Emory University (2007)

Professional Education


  • B.ChE., Georgia Institute of Technology, Chemical Engineering (1999)
  • Doctor of Philosophy, Emory University (2010)

Stanford Advisors


Publications

Journal Articles


  • Branched signal wiring of an essential bacterial cell-cycle phosphotransfer protein. Structure Blair, J. A., Xu, Q., Childers, W. S., Mathews, I. I., Kern, J. W., Eckart, M., Deacon, A. M., Shapiro, L. 2013; 21 (9): 1590-1601

    Abstract

    Vital to bacterial survival is the faithful propagation of cellular signals, and in Caulobacter crescentus, ChpT is an essential mediator within the cell-cycle circuit. ChpT functions as a histidine-containing phosphotransfer protein (HPt) that shuttles a phosphoryl group from the receiver domain of CckA, the upstream hybrid histidine kinase (HK), to one of two downstream response regulators (CtrA or CpdR) that controls cell-cycle progression. To understand how ChpT interacts with multiple signaling partners, we solved the crystal structure of ChpT at 2.3 Å resolution. ChpT adopts a pseudo-HK architecture but does not bind ATP. We identified two point mutation classes affecting phosphotransfer and cell morphology: one that globally impairs ChpT phosphotransfer, and a second that mediates partner selection. Importantly, a small set of conserved ChpT residues promotes signaling crosstalk and contributes to the branched signaling that activates the master regulator CtrA while inactivating the CtrA degradation signal, CpdR.

    View details for DOI 10.1016/j.str.2013.06.024

    View details for PubMedID 23932593

  • Peptides Organized as Bilayer Membranes ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Childers, W. S., Mehta, A. K., Ni, R., Taylor, J. V., Lynn, D. G. 2010; 49 (24): 4104-4107

    View details for DOI 10.1002/anie.201000212

    View details for Web of Science ID 000278796400021

    View details for PubMedID 20425875

  • Templating Molecular Arrays in Amyloid's Cross-beta Grooves JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Childers, W. S., Mehta, A. K., Lu, K., Lynn, D. G. 2009; 131 (29): 10165-10172

    Abstract

    Amyloid fibers, independent of primary amino acid sequence, share a common cross-beta structure and bind the histochemical dye Congo Red (CR). Despite extensive use of CR in amyloid diagnostics, remarkably little is known about the specific and characteristic binding interactions. Fibril insolubility, morphological inhomogeneity, and multiple possible ligand binding sites all conspire to limit characterization. Here, we have exploited the structure of cross-beta nanotubes, which limit the number of potential binding sites, to directly interrogate cross-beta laminate grooves. CR bound to cross-beta nanotubes displays the hallmark apple-green interference color, a broad red-shifted low energy transition, and a K(d) of 1.9 +/- 0.5 microM. Oriented electron diffraction and linear dichroism defines the orientation of CR as parallel to the amyloid long axis and colinear with laminate grooves. The broad red-shifted UV signature of CR bound to amyloid can be explained by semiempirical quantum calculations that support the existence of a precise network of J- and H-CR aggregates, illuminating the ability of the amyloid to organize molecules into extended arrays that underlie the remarkable diagnostic potential of CR.

    View details for DOI 10.1021/ja902332s

    View details for Web of Science ID 000268395000064

    View details for PubMedID 19569651

  • Facial symmetry in protein self-assembly JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Mehta, A. K., Lu, K., Childers, W. S., Liang, Y., Dublin, S. N., Dong, J., Snyder, J. P., Pingali, S. V., Thiyagarajan, P., Lynn, D. G. 2008; 130 (30): 9829-9835

    Abstract

    Amyloids are self-assembled protein architectures implicated in dozens of misfolding diseases. These assemblies appear to emerge through a "selection" of specific conformational "strains" which nucleate and propagate within cells to cause disease. The short Abeta(16-22) peptide, which includes the central core of the Alzheimer's disease Abeta peptide, generates an amyloid fiber which is morphologically indistinguishable from the full-length peptide fiber, but it can also form other morphologies under distinct conditions. Here we combine spectroscopic and microscopy analyses that reveal the subtle atomic-level differences that dictate assembly of two conformationally pure Abeta(16-22) assemblies, amyloid fibers and nanotubes, and define the minimal repeating unit for each assembly.

    View details for DOI 10.1021/ja801511n

    View details for Web of Science ID 000257902500044

    View details for PubMedID 18593163

  • Phase Networks of Cross-beta Peptide Assemblies LANGMUIR Childers, W. S., Anthony, N. R., Mehta, A. K., Berland, K. M., Lynn, D. G. 2012; 28 (15): 6386-6395

    Abstract

    Recent evidence suggests that simple peptides can access diverse amphiphilic phases, and that these structures underlie the robust and widely distributed assemblies implicated in nearly 40 protein misfolding diseases. Here we exploit a minimal nucleating core of the A? peptide of Alzheimer's disease to map its morphologically accessible phases that include stable intermolecular molten particles, fibers, twisted and helical ribbons, and nanotubes. Analyses with both fluorescence lifetime imaging microscopy (FLIM) and transmission electron microscopy provide evidence for liquid-liquid phase separations, similar to the coexisting dilute and dense protein-rich liquid phases so critical for the liquid-solid transition in protein crystallization. We show that the observed particles are critical for transitions to the more ordered cross-? peptide phases, which are prevalent in all amyloid assemblies, and identify specific conditions that arrest assembly at the phase boundaries. We have identified a size dependence of the particles in order to transition to the para-crystalline phase and a width of the cross-? assemblies that defines the transition between twisted fibers and helically coiled ribbons. These experimental results reveal an interconnected network of increasing molecularly ordered cross-? transitions, greatly extending the initial computational models for cross-? assemblies.

    View details for DOI 10.1021/la300143j

    View details for Web of Science ID 000302852200023

    View details for PubMedID 22439620

  • Remodeling Cross-beta Nanotube Surfaces with Peptide/Lipid Chimeras ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Ni, R., Childers, W. S., Hardcastle, K. I., Mehta, A. K., Lynn, D. G. 2012; 51 (27): 6635-6638

    View details for DOI 10.1002/anie.201201173

    View details for Web of Science ID 000305987900015

    View details for PubMedID 22736642

  • Peptide membranes in chemical evolution CURRENT OPINION IN CHEMICAL BIOLOGY Childers, W. S., Ni, R., Mehta, A. K., Lynn, D. G. 2009; 13 (5-6): 652-659

    Abstract

    Simple surfactants achieve remarkable long-range order in aqueous environments. This organizing potential is seen most dramatically in biological membranes where phospholipid assemblies both define cell boundaries and provide a ubiquitous structural scaffold for controlling cellular chemistry. Here we consider simple peptides that also spontaneously assemble into exceptionally ordered scaffolds, and review early data suggesting that these structures maintain the functional diversity of proteins. We argue that such scaffolds can achieve the required molecular order and catalytic agility for the emergence of chemical evolution.

    View details for DOI 10.1016/j.cbpa.2009.09.027

    View details for Web of Science ID 000272984600022

    View details for PubMedID 19879180

  • Nucleobase-Directed Amyloid Nanotube Assembly JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Liu, P., Ni, R., Mehta, A. K., Childers, W. S., Lakdawala, A., Pingali, S. V., Thiyagarajan, P., Lynn, D. G. 2008; 130 (50): 16867-?

    Abstract

    Cytosine nucleobases were successfully incorporated into the side chain of the self-assembling amyloid peptide fragment HHQALVFFA to give ccAQLVFFA. At a pH range of 3-4, where cytosine is expected to be partially protonated, small-angle X-ray scattering analyses revealed the nucleobase peptide assembles to be well-defined nanotubes with an outer diameter of 24.8 nm and wall thicknesses of 3.3 nm. FT-IR and X-ray diffraction confirmed beta-sheet-rich assembly with the characteristic cross-beta architecture of amyloid. The beta-sheet registry, determined by measuring (13)CO-(13)CO backbone distances with solid-state NMR and linear dichroism, placed the cytosine bases roughly perpendicular to the nanotube axis, resulting in a model where the complementary interactions between the cytosine bases increases beta-sheet stacking to give the nanotube architecture. These scaffolds then extend the templates used to encode biological information beyond the nucleic acid duplexes and into covalent networks whose self-assembly is still defined by a precise complementarity of the side-chain registry.

    View details for DOI 10.1021/ja807425h

    View details for Web of Science ID 000263320400020

    View details for PubMedID 19053426

  • Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Dong, J., Canfield, J. M., Mehta, A. K., Shokes, J. E., Tian, B., Childers, W. S., Simmons, J. A., Mao, Z., Scott, R. A., Warncke, K., Lynn, D. G. 2007; 104 (33): 13313-13318

    Abstract

    Protein and peptide assembly into amyloid has been implicated in functions that range from beneficial epigenetic controls to pathological etiologies. However, the exact structures of the assemblies that regulate biological activity remain poorly defined. We have previously used Zn(2+) to modulate the assembly kinetics and morphology of congeners of the amyloid beta peptide (Abeta) associated with Alzheimer's disease. We now reveal a correlation among Abeta-Cu(2+) coordination, peptide self-assembly, and neuronal viability. By using the central segment of Abeta, HHQKLVFFA or Abeta(13-21), which contains residues H13 and H14 implicated in Abeta-metal ion binding, we show that Cu(2+) forms complexes with Abeta(13-21) and its K16A mutant and that the complexes, which do not self-assemble into fibrils, have structures similar to those found for the human prion protein, PrP. N-terminal acetylation and H14A substitution, Ac-Abeta(13-21)H14A, alters metal coordination, allowing Cu(2+) to accelerate assembly into neurotoxic fibrils. These results establish that the N-terminal region of Abeta can access different metal-ion-coordination environments and that different complexes can lead to profound changes in Abeta self-assembly kinetics, morphology, and toxicity. Related metal-ion coordination may be critical to the etiology of other neurodegenerative diseases.

    View details for DOI 10.1073/pnas.0702669104

    View details for Web of Science ID 000248899600020

    View details for PubMedID 17686982

  • Macroscale assembly of peptide nanotubes CHEMICAL COMMUNICATIONS Lu, K., Guo, L., Mehta, A. K., Childers, W. S., Dublin, S. N., Skanthakumar, S., Conticello, V. P., Thiyagarajan, P., Apkarian, R. P., Lynn, D. G. 2007: 2729-2731

    Abstract

    Simple oligopeptides that self-assemble into homogeneous nanotubes can be directed to further assemble into macroscale parallel arrays through protein "salting out" strategies.

    View details for DOI 10.1039/b701029j

    View details for Web of Science ID 000247543000029

    View details for PubMedID 17594035

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