Prof. David S. Talaga, Ph.D.

Research Interests: Protein Folding, Protein and Peptide Conformational Dynamics, Protein Aggregation, Amyloid, Parkinson’s Disease, Amyloidoses, Nanopores, Single Molecule Fluorescence, Ultrafast Spectroscopy, Information Theory, Bayesian Statistics, Global Data Analysis, Statistical Mechanics.

Name: David Talaga

Occupation: Professor/Principal Investigator

Education: A.B. Occidental College — Ph.D. UCLA — Postdoc U Pennsylvania

Research Interests: Protein Folding, Protein Aggregation, Amyloid, Parkinson’s Disease, Amyloidoses, Nanopores, Single Molecule Fluorescence, Ultrafast Spectroscopy, Information Theory, Bayesian Statistics, Global Data Analysis, Statistical Mechanics.

Courses Taught: General Chemistry, Analytical Chemistry, Physical Chemistry, Spectroscopy, Group Theory, Statistical Mechanics, Statistical Thermodynamics, Biophysical Chemistry, General Education Chemistry.

Favorite journals: J Phys Chem, JACS, PNAS, Biophys J, JMB, J Chem Phys, Anal Chem.

Personal Interests: Swing Dancing, Opera, Theater, Jazz, Argentine Tango, Minor League Baseball, Sailing, Winemaking.

Research Summary: Prof. Talaga's research program focuses on the heterogeneity in protein conformation, particularly as proteins aggregate into various intermediates that lead to amyloid formation. Prof. Talaga's group develops measurements that can distinguish protein conformation through different aggregation states. A significant part of their efforts includes solving experimental and theoretical challenges that arise in measuring and interpreting such heterogeneous systems. These problems not only confound characterization of amyloidogenesis, but also appear in most protein systems, making these ancillary developments important to many other fields.

Important Discoveries & New Methods Introduced:
  • Theoretical framework for relating electrochemical impedance spectroscopy to protein structure.
  • Determination of nanopore geometry using electrochemical impedance spectroscopy.
  • Use of solid state nanopores to probe protein aggregation at the single molecule level. 
  • Discovery of Protein Stall Points arising from local charge effects in translocating proteins.
  • Identification of protein unfolding during nanopore translocation. 
  • Identification of the role of hydrophobic interfaces in the aggregation of alpha-synuclein
  • Introduction of a free energy landscape formalism to model amyloid formation kinetics.
  • Use of umbrella sampling MD simulations to model fluorescent protein conjugates.
  • Identification of multiple ligand binding modes in ß-lactoglobulin via fluorescence lifetime and stokes shift. 
  • Use of AFM to determine protein aggregation distributions.
  • Hidden Markov models to analyze single molecule fluorescence.
  • Shannon Information Theory to determine the resolution limits of photon-based single-molecule measurements.
  • Step-wise photobleaching for chromophore counting.
  • Novel global fitting regularization by population continuity.

Molecular-Level Mechanisms of Amyloidogenesis.The study of amyloid structure and growth has been motivated by their implication in many human diseases. There are ~20 diseases associated with excessive deposits of amyloid plaques in the affected tissue or organ including Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes, and spongiform encephalopathies. In these disease states, proteins that are normally soluble undergo aggregation to form various intermediates and amyloidogenic species. These species subsequently assemble to generate insoluble fibrils that accumulate in the affected tissues or organs. A detailed understanding of amyloid growth mechanisms will allow new approaches to the prevention of amyloid formation and better diagnostics for early detection of amyloidogenic diseases.

A molecular-level mechanism of how the different amyloid species interconvert is the goal of this project. There are many species of amyloid particles present physiologically. Our single molecule studies aim to classify the species involved in amyloid formation according to size, shape, kinetic reactivity, and monomer 2° and 3° structural information. A molecular-level mechanism of amyloid growth must include details as to when the protein misfold occurs and how it is influenced by the dynamics of protein structure. To determine the physical interactions and structural changes involved in the amyloid assembly mechanism, we study effect of environmental variables such as temperature, pH, helix promoting solvents, denaturants, and reducing agents. The environmental effect on aggregation is expected to be species-dependent reflecting a possible hierarchy of structural interactions.

Nanopore Measurements of Proteins The use of the resistive pulse method to determine the size of microscopic particles in a small pore dates back to Coulter in the 1950's. Recently nanofabrication of single pores with nanometer dimensions has enabled similar studies of single molecules. The Talaga group has been collaborating with the Li group at U. Arkansas to make measurements on proteins under amyloidogenic conditions, with the goal of measuring the shape and size distribution of aggregation intermediates. The ultimate goal of this research is to provide single molecule equivalents to the existing battery of gel electrophoretic methods. These nanopore methods would determine the number and type of proteins in samples the size of a single cell and provide real-time monitoring of the assembly of multi-protein structures. The short-term objectives are to:

  • use nanopores to distinguish proteins based on coarse-grain differences (10-30 amino acid stretches) in their primary sequence,
  • evaluate competing models of the translocation physics, 
  • develop electrochemical impedance spectroscopy as a method to determine nanopore shape and size and evaluate the interactions between protein and the nanopore, 
  • identify the nanopore geometries that are most suitable for protein identification, 
  • optimize the physical and chemical treatment of the nanopore surface for measurement of proteins, and 
  • develop new nanopore measurements that do not disrupt protein assemblies.

Information theory, global data analysis, statistics.

Biography: David Talaga was born in Des Moines, Iowa. He grew up in Iowa, Illinois, New York, Michigan, and California, attending some eleven different schools for his primary education. In spite of a disjointed education, he developed an early love for science and etymology and read reference books for fun. David attended Damien High School in La Verne, California which is a Catholic Boys High School run by priests of the Congregation of the Sacred Hearts of Jesus and Mary. While there he was active in Model United Nations and proved himself a mediocre athlete in five different sports. His fascination with science continued, but he also became interested in education through his experiences tutoring math and science. He picked up computer programming first as a hobby and then through coursework. Shortly before he graduated in 1987 he won the Science Gold Medal in the regional Academic Olympiad and the Damien AP Physics Award.

David received his undergraduate degree in chemistry and mathematics from Occidental College and supplemented his interests with graduate courses from Caltech. He started working in the laboratory of Prof. Craney as a freshman, and continued there until his graduation in 1991. In the Craney lab, David studied the human erythrocyte protein glucose 6-phosphate dehydrogenase. This included isolation and purification of the enzyme from gallons of past-code human blood cells, performing inhibition kinetics studies and 31P NMR substrate binding studies. While at Occidental he served as vice president of the local chapter of the Alpha Chi Sigma chemistry fraternity. He worked at the Learning Resource Center as a Peer Advisor in General, Analytcal, and Physical Chemistry, and served as a Teaching Assistant for General and Analytical Chemistry. He started a volunteer tutoring program that significantly increased the number of students show could receive extra help in chemistry and biology. These efforts also enhanced the interaction between student in the earlier and later years of their undergraduate experience. He also served as a representative in student government. These experiences cemented his interest in research and teaching in physical chemistry.

David Talaga was seduced away from biochemistry by the beautiful symmetry of inorganic and organometallic molecules and joined the laboratory of Jeff Zink at UCLA to study for his PhD. At UCLA David studied high-resolution gas phase spectroscopy of inorganic complexes and chemical vapor deposition precursors. He also developed time-dependent quantum theoretical approaches to vibronic coupling effects on electronic and vibrational spectroscopy and filed his dissertation in the fall of 1996. He worked as a TA in general chemistry lecture and laboratory courses, in Physical chemistry, in Graduate Group Theory, and in the Computer Laboratory where the Chemistry Department’s early efforts to integrate computer simulations and tutorials into the undergraduate curriculum was implemented. David also took on the role of Workshop Facilitator in the UCLA Math and Science Scholars program.

In late 1996, David Talaga was awarded a NIH NRSA postdoctoral fellowship to train under Robin Hochstrasser at the University of Pennsylvania. At Penn, David returned to biophysical problems and worked on picosecond temperature jump methods for initiation of conformational changes and protein unfolding monitored using infrared spectroscopy. He also worked on single molecule FRET approaches to protein folding.

After Penn Dr. Talaga joined the faculty at Rutgers New Brunswick, where he attained the rank of Associate Professor of Chemistry and Chemical Biology and maintains an appointment as a member of the Graduate Faculty. He is currently an Associate Professor at Montclair State University. His research has focussed on amyloidogenesis, single molecule experiments and theory, and protein folding. He has recently been working on incorporating nanopore approaches to single protein folding.





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