Meet the Han Lab

Spectroscopy of Biological and Materials Surfaces and Interactions

A concerted effort of my research group is the development of novel techniques and approaches, relying on electron and nuclear spin magnetic resonance that enables the study of biomolecular structure, dynamics and interaction with unprecedented sensitivity, resolution and information content. My lab takes a two-pronged approach: (1) to develop new instrumentation and methods, and (2) to pursue critical, outstanding, questions in biophysics and materials science whose resolution requires unconventional technical approaches and convincing new data. We witness time and time again the power of “Seeing is Believing”. The direct experimental observation of dramatic conformational changes around signature hydrophobic regions of Tau when subject to aggregating conditions, offers a strong basis for the conformation-pathology hypothesis for Tau—an intrinsically disordered protein (IDP) implicated in devastating neurodegenerative diseases, including Alzheimer’s disease. The observation of water retardation at a liposome surface, reporting on the expected binding constant of a surface-active constituent upon titration proves surface adsorption, which is particularly meaningful if conventional signatures signifying binding such as calorimetric changes are absent. These are critical measurement capabilities, as weak biomolecular interactions are both prevalent and important in mediating protein function that are, however, difficult to capture. A core focus of my lab’s development is dynamic nuclear polarization (DNP) that amplifies the nuclear magnetic resonance (NMR) signal by several orders of magnitudes, by transferring polarization from highly polarized electron spin probes to the surrounding nuclei. We employ strategic spin probes at biomolecular sites or surfaces, and pursue ambient temperature Overhauser DNP of hydration dynamics at 10 GHz, as well as solid-state magic angle spinning and static DNP NMR at 200 GHz at cryogenic temperatures. Concurrently, we develop cw and pulsed electron paramagnetic resonance (EPR) capabilities at > 200 GHz and arbitrary waveform generation (AWG) pulsed EPR for the study of biomolecular structure and dynamics, as well as utilize pulsed double electron electron resonance (DEER) methods.

In one of our priority projects, we utilize Overhauser DNP to site-specifically detect surface water dynamics on a protein surface with tens to hundreds of picosecond correlation times, within 5-10 Å of the spin probe tethered to a protein site. Interfacial water dynamics have been shown to be an exceptionally sensitive reporter of conformational changes of proteins, as demonstrated with protein folding, protein binding and allosteric events. Core questions of interest to my group are directed towards the study of lipid membrane properties, their role in protein structure, assembly and function, the functional role of protein-coupled water, the mechanism of IDP aggregation and its connection to tau pathology, and the fluid-fluid phase separation of protein polyelectrolytes to droplets, also termed complex coacervates, and their biological roles. We made crucial discoveries of dramatic conformational changes and intermediate formation occurring in the earliest aggregation stages of Tau proteins, preceding fibril formation. Our long-term goal is to discover the pathological Tau conformations and relevant pathways that drive Tau aggregation.

The main research activities in the Han lab can be broadly categorized into:

  1. Neurodegenerative Diseases and Intrinsically Disordered Proteins
  2. Membrane Protein Organization and Function
  3. Role of Hydration Water in Biology
  4. Role of Surface Chemistry in Transport, Energy to Catalysis
  5. DNP and EPR Instrument and Methods Development

In short, an ambitious and general goal of the laboratory is to turn NMR from a bulk to a surface characterization tool, and in doing so access entirely novel information content and research utility in materials science and the biochemistry/biophysics of complex biomolecular systems. Find out more about our current work in the research section, or click on the publications tab to see what has been done so far.

We are overjoyed to announce that Alisa Leavesley has finished her PhD study on instrument development in dynamic nuclear polarization.

We are pleased to announce that Kendrick (Khanh) Nguyen has passed his candidacy exam.

A conference at UCSB will explore new possibilities in transformational science across disciplines.

UCSB’s terahertz free-electron laser is the only facility of its kind in the U.S.