Ka Yee C. Lee

Scholar: 1999

Awarded Institution
The University of Chicago
Department of Chemistry


Research Interests

Lipid-Protein Interactions

A wide variety of diseases are results of deficient or abnormal protein-lipid interactions. The elucidation of the interactions between specific proteins and lipids, and the ability to examine and manipulate biomembranes that mimic real life systems hold the key to a better understanding of these diseases. Our research interests lie in the interdisciplinary area which can be termed as "interfacial medicine". Using two-dimensional monolayers, either at the air-water interface or transferred onto solid substrates, and supported bilayers as model systems, along with various microscopy and scattering techniques, we plan to carry out fundamental studies on the interactions between lipids and proteins to gain insights into the biophysical aspects of these diseases. Two diseases of particular interest are listed below.

Lung Surfactant System and Respiratory Distress Syndrome (RDS)

A complex mixture of lipids and proteins, known as lung surfactant, forms monolayers at the alveolar air-water interface. The surfactant lowers the surface tension to near zero, and is responsible for reducing the work of breathing. A lack of surfactant, either due to immaturity in premature infants or disease or trauma in adults, can result in RDS. In spite of the serious morbidity and mortality of the disease, a firm understanding of the role of surfactant in both normal and diseased lungs is still lacking. My group is interested in developing a detailed structure-function relationship for the various components of lung surfactant. In particular, we will examine the phase behavior of various mixtures of lung surfactant components, as well as the interactions between lung surfactant specific proteins and the surrounding lipid matrix. We will explore the effect of lung surfactant proteins on monolayer collapse dynamics, and the effect of serum proteins on the normal functioning of the lung surfactant. The knowledge gained from this should lead to an understanding of the morphological consequences of monolayer phase separation and collapse, which is necessary for the continued development of positive interventions for patients suffering from RDS.

Amyloid beta (A-beta) Peptides and Alzheimer's Disease

A-beta, a self-assembling 39-43 residue peptide generated by the proteolytic processing of the amyloid precursor protein, comprises the major proteinaceous component of neuritic plaques and vascular deposits that appear in Alzheimer_s disease, and is implicated as one of the causal factors in the pathology of the disease. Since the Ab peptide fragment includes 28 residues just outside the membrane plus the first 11-15 residues of the transmembrane domain, it has been shown to display properties commonly associated with surfactants. My group is interested in understanding the aggregation of the A-beta peptides, and in using two-dimensional thin films (either free-standing monolayers or supported bilayers) as "templates" to explore the possibility of surface-induced aggregation. We plan to study various isoforms of A-beta and examine their surface activities and their association with model membrane systems in both their monomeric and aggregated states. This can elucidate the residue length dependence of the aggregation process, and help explain why the longer A-beta isoforms may be more intimately associated with Alzheimer's disease pathology than their shorter counterparts. A-beta is also known to aggregate and form fibrils, though the mechanism involved is still not well understood. Since the rate of this process can be adjusted by various experimental parameters, we plan to monitor the formation process, and characterize the structure of the fibrils formed. Our goal is to provide a model for A-beta aggregation.

Other research interests of the group includes protein and lipid diffusion in model membrane systems, structures and dynamics of monolayer domains, and the manipulation of supported bilayers via electric field.