About

Rosina M. Georgiadis is an Associate Professor in the Department of Chemistry at Boston University. Her research focuses on developing experimental tools to characterize biomolecular binding at surfaces and in solution, involving interactions with proteins, oligonucleotides, small molecules, bioconjugates, or nanoparticles. She employs methods such as surface plasmon resonance (SPR) spectroscopy, surface acoustic wave (SAW) sensing, and fluorescence-based microscale thermophoresis (MST) to determine the kinetics and thermodynamics of binding, as well as electric field effects on binding at interfaces. Her graduate research involved exploring ion/molecule reactions using mass spectrometry, and her post-doctoral work investigated electronic structure at electrochemical interfaces using non-linear optics. Prof. Georgiadis teaches both introductory and advanced chemistry courses. In 2013, she developed a new advanced instrumental methods of analysis lab course and pioneered the integration of cloud-enabled student access to instrument software, which was featured in a 2017 Chemical and Engineering News article and further described in a 2018 publication. She was honored in 2019 with the Gerald and Deanne Gitner Family Award for Innovation in Teaching with Technology at Boston University. She is actively working to expand her cloud-based access approach to other courses, disciplines, and institutions.

Research topics

• Chemistry
• Materials science
• Computer science
• Optics
• Atomic physics

Selected publications

• Cutting the cord: virtual machines for real instrumental analysis not just at the instrument

  Analytical and Bioanalytical Chemistry · 2018-03-14 · 1 citations

  article1st authorCorresponding
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• Virtual machines: A new way to teach transferable skills in the advanced undergraduate laboratory

  OpenBU (Boston University) · 2018-07-29

  article1st authorCorresponding
  Publisher

• Comprehensive Experimental and Computational Analysis of Binding Energy Hot Spots at the NF-κB Essential Modulator/IKKβ Protein–Protein Interface

  Journal of the American Chemical Society · 2013-03-18 · 47 citations

  article

  We report a comprehensive analysis of binding energy hot spots at the protein-protein interaction (PPI) interface between nuclear factor kappa B (NF-κB) essential modulator (NEMO) and IκB kinase subunit β (IKKβ), an interaction that is critical for NF-κB pathway signaling, using experimental alanine scanning mutagenesis and also the FTMap method for computational fragment screening. The experimental results confirm that the previously identified NEMO binding domain (NBD) region of IKKβ contains the highest concentration of hot-spot residues, the strongest of which are W739, W741, and L742 (ΔΔG = 4.3, 3.5, and 3.2 kcal/mol, respectively). The region occupied by these residues defines a potentially druggable binding site on NEMO that extends for ~16 Å to additionally include the regions that bind IKKβ L737 and F734. NBD residues D738 and S740 are also important for binding but do not make direct contact with NEMO, instead likely acting to stabilize the active conformation of surrounding residues. We additionally found two previously unknown hot-spot regions centered on IKKβ residues L708/V709 and L719/I723. The computational approach successfully identified all three hot-spot regions on IKKβ. Moreover, the method was able to accurately quantify the energetic importance of all hot-spot residues involving direct contact with NEMO. Our results provide new information to guide the discovery of small-molecule inhibitors that target the NEMO/IKKβ interaction. They additionally clarify the structural and energetic complementarity between "pocket-forming" and "pocket-occupying" hot-spot residues, and further validate computational fragment mapping as a method for identifying hot spots at PPI interfaces.

  PublisherDOI

• Use of Angle‐Resolved Surface Plasmon Resonance Imaging (SPRi) for the Characterization of Protein Binding Dynamics

  The FASEB Journal · 2011-04-01

  articleSenior author

  Protein‐protein interactions are essential at almost every level of cellular function. Although structures of various protein complexes have been characterized, the mechanisms involved in protein binding events and the transient dynamics of complex formation are not fully understood. Here we present an improved angle‐resolved surface plasmon resonance imaging (SPRi) methodology that allows real time multi‐array kinetic and thermodynamic analysis of protein binding events on surfaces. Using Tumor Necrosis Factor alpha (TNFα), a homotrimeric protein, as a test system we have developed surface fabrication techniques including multi‐channel microfluidic delivery systems and patterning capabilities, and have employed various surface immobilization strategies to investigate the influences of density, orientation, and heterogeneity of surface immobilized TNFα on protein binding efficiency and kinetics. A unique multi‐wavelength SPRi approach is utilized to simultaneously determine dielectric constants and thicknesses of TNFα layers, allowing characterization of the oligomeric structure of the immobilized trimer. Results showed that TNFα activity for known binding partner TNFR2, as well as TNFα subunit dissociation dynamics, were highly dependent on the selected immobilization conditions. This work was supported by NIGMS and Boston University, Department of Chemistry.

  PublisherDOI

• Distance- and Wavelength-Dependent Dielectric Function of Au Nanoparticles by Angle-Resolved Surface Plasmon Resonance Imaging

  The Journal of Physical Chemistry C · 2010-04-27 · 32 citations

  articleSenior author

  The optical properties of nanoparticles (NPs) near metal surfaces must be better understood in order to fully exploit their signal-enhancing capabilities in optical biosensors, such as in surface plasmon resonance studies. We use angle-resolved SPR imaging and a modified Maxwell−Garnett model to determine the optical properties of 10-nm-diameter gold NPs deposited on planar Au coated with various thicknesses of SiO2. We investigate how the intrinsic NP dielectric constants and extinction coefficients vary as a function of particle-to-metal-substrate distance (dP−S) for short distances that span the dimension of the NP (0−26 nm) and as a function of excitation wavelength (λexc) for values that span the NP absorbance spectrum. When the NPs are deposited almost directly onto the Au substrate, the NP dielectric function shows anomalous dispersion. At distances far from the planar Au, normal dispersion is observed. The distance dependence, viewed in terms of extinction coefficients, is consistent with a red shift in the NP absorption as dP−S decreases. Although this shift has been predicted and observed, the distance dependence of the intrinsic NP dielectric function is not known. Indeed, NP dielectric functions, which are exquisitely sensitive to experimental conditions, are generally not available. Such fundamental NP properties are needed for quantitative applications in high-sensitivity refractive-index-based biosensors and may also be useful for testing theoretical models.

  PublisherDOI

• Quantitative Surface Plasmon Resonance Imaging: A Simple Approach to Automated Angle Scanning

  Analytical Chemistry · 2008-05-14 · 36 citations

  articleSenior author

  Here we present an automated angle-scanning surface plasmon resonance imaging (SPRi) instrument which provides multiplexed, quantitative reflectance data over a wide angular range. Angle-dependent artifacts, which arise from the simple optical setup, are corrected using software. This enables monitoring of significantly different surface coatings in many solvents, which would be outside the dynamic range of typical fixed-angle instruments. Operation in the visible to near-infrared range without the need for reconfiguration extends the instrument capabilities to increase sensitivity or to investigate the optical properties of surface films. This instrument provides maximum flexibility to study a wide range of systems with full exploitation of the quantitative capabilities of SPRi achieved by fitting data to the Fresnel model.

  PublisherDOI

• In-situ fluorescence spectroscopy of self-assembled monolayers of HS-(CH2)n-fluorescein and HS-(CH2)6-poly(dT)18-fluorescein at gold electrodes under cyclic voltammetric conditions

  Journal of Electroanalytical Chemistry · 2008-05-14 · 8 citations

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• Kinetic Discrimination of Sequence-Specific DNA−Drug Binding Measured by Surface Plasmon Resonance Imaging and Comparison to Solution-Phase Measurements

  Journal of the American Chemical Society · 2007-08-01 · 49 citations

  articleSenior author

  We demonstrate the use of surface plasmon resonance (SPR) imaging for direct detection of small-molecule binding to surface-bound DNA probes. Using a carefully designed array surface, we quantitatively discriminate between the interactions of a model drug with different immobilized DNA binding sites. Specifically, we measure the association and dissociation intercalation rates of actinomycin-D (ACTD) to and from double-stranded 5'-TGCT-3' and 5'-GGCA-3' binding sites. The rates measured provide mechanistic information about the DNA-ACTD interaction; ACTD initially binds nonspecifically to DNA but exerts its activity by dissociating slowly from strong affinity sites. We observe a slow dissociation time of kd-1 = 3300 +/- 100 s for ACTD bound to the strong affinity site 5'-TGCT-3' and a much faster dissociation time (210 +/- 15 s) for ACTD bound weakly to the site 5'-GGCA-3'. These dissociation rates, which differ by an order of magnitude, determine the binding affinity for each site (8.8 x 10(6) and 1.0 x 10(6) M(-1), respectively). We assess the effect the surface environment has on these biosensor measurements by determining kinetic and thermodynamic constants for the same DNA-ACTD interactions in solution. The surface suppresses binding affinities approximately 4-fold for both binding sites. This suppression suggests a barrier to DNA-drug association; ACTD binding to duplex DNA is approximately 100 times slower on the surface than in solution.

  PublisherDOI

• Quantitative Angle-Resolved SPR Imaging of DNA−DNA and DNA−Drug Kinetics

  Journal of the American Chemical Society · 2005-11-16 · 83 citations

  articleSenior author

  We demonstrate the quantitative characterization of DNA-DNA and DNA-drug interactions by angle-resolved surface plasmon resonance (SPR) imaging. Combining the angle-scanning capabilities of traditional SPR with the spatial definition capabilities of imaging, we directly measure DNA and drug surface coverages and kinetics simultaneously for multiple patterned spots. We find excellent agreement of DNA-DNA hybridization kinetics and thermodynamics measured by both the imaging system and traditional SPR. Instrument response and sensitivity is further demonstrated by successful measurement of association and dissociation kinetics of actinomycin-D binding to a low-density doubled-stranded DNA binding sequence. Without independent calibration, analysis of angle-resolved SPR imaging data yields 2.9 +/- 0.1 drugs per duplex at saturation coverage, consistent with all available duplex binding sites being occupied.

  PublisherDOI

• Sequence-Dependent DNA Immobilization:  Specific versus Nonspecific Contributions

  Langmuir · 2004-03-03 · 106 citations

  articleSenior author

  We present results of the first systematic study on in situ sequence-dependent kinetics for short single-strand oligonucleotide surface immobilization. By measuring film coverage for both thiolated and nonthiolated homo-oligomers as a function of adsorption time, we determine the relative contribution of specific thiol-surface and nonspecific DNA-surface interactions to the overall mechanism of DNA-thiol attachment to gold. We find that sequence-dependent nonspecific surface interactions play a significant role in DNA-thiol immobilization, influencing not only the kinetics but also the extent of oligomer adsorption. For example, sequences that initially form strong, rapid nonspecific contacts with the surface hinder long-time thiol adsorption (i.e., poly(dA)-thiol). In contrast, sequences with nucleotides that initially bind slowly and weakly to the surface (i.e., poly(dT)-thiol) do not obstruct further thiol adsorption, resulting in higher film coverage and Langmuir immobilization kinetics. This view of the DNA-thiol immobilization mechanism is further supported by sequence-dependent rinsing losses observed for thiolated DNA strands but not for analogous nonthiolated strands. Nonthiolated strands contact the surface strongly in a more horizontal orientation, whereas thiolated strands attain a more upright orientation that allows vertical DNA-DNA base-stacking. The results clearly illustrate the importance and interplay of competitive specific and nonspecific forces in forming DNA-thiol films. The specific coverage attained and the time dependence of the adsorption process depend on the prevailing sequence composition.

  PublisherDOI

Recent grants

• Multichannel Surface Plasmon Resonance for Quantitative Biomolecular Kinetics

  NSF · $410k · 2001–2005

• NIH Grant R01CA089562

  NIH · $798k · 2006

Frequent coauthors

• P. B. Armentrout

  University of Utah

  14 shared

• Kevin A. Peterlinz

  Boston University

  10 shared

• Alexander W. Peterson

  Cancer Institute (WIA)

  8 shared

• Ellen R. Fisher

  University of New Mexico

  6 shared

• Richard Bradley

  5 shared

• John E. Bartmess

  University of Tennessee at Knoxville

  5 shared

• Geraldine L. Richmond

  5 shared

• N. Aristov

  4 shared

Education

• Ph.D., not specified

  not specified

• M.S., not specified

  not specified

• B.S., not specified

  not specified

Awards & honors

• Gerald and Deanne Gitner Family Award for Innovation in Teac…