Research Interests

Intermolecular Interactions in Membranes

A study of biological membrane dynamics and organization via the use of synthetic lipid molecular probes

The research interests in my group are centered around membrane structure and function.  We use a variety of chemical and biophysical techniques (i.e., organic synthesis together with calorimetric, spectral, and photoaffinity methods) to examine the interactions of lipids with each other and with membrane-bound proteins of biological significance (such as the E1 glycoprotein of enveloped viruses and the G-protein coupled receptors that recognize sphingolipids and lysophosphatidic acids).  We are interested in determining the intracellular distribution of lipids in cell membranes and the transbilayer distribution of cerebrosides in model membranes. 

Emphasis is currently being placed in my laboratory on sphingolipids, which play important roles in the maintenance of cell membrane and lipoprotein structure and in the regulation of various cell signaling transduction pathways. We are particularly interested in the chemical synthesis of lipids with biological properties. Our approach is to synthesize chemically homogeneous sphingolipid analogs with isotopic, fluorescent, or photoreactive labels in order to probe the processes outlined above and thereby determine what specific sites in the sphingolipid molecule play a role in the specific membrane-related process under investigation. We have also discovered unnatural ceramides that possess anticancer activity in vitro.

Another area of interest is the development of new synthetic methodology for the compounds described above.  We often synthesize unnatural lipids in an effort  to gain an understanding of the mechanisms of action of natural bioactive lipids at the molecular level.

An overview of some of our recent research appears in the following article:

R. Bittman, “The 2003 ASBMB-Avanti Award in Lipids Address: Applications on Novel Synthetic Lipids to Biological Problems,” Chem. Phys. Lipids 129, 111-131 (2004).

The theme of this award address was to illustrate the power of synthetic organic chemistry as applied to the preparation and use of  unnatural lipid analogs.  Specific questions involving membrane-related problems in cell biology, pharmacology, and biophysics were answered using the novel synthetic lipids.

The term "sphingolipids" was coined by J. L. W. Thudichum (1828-1901), the father of sphingolipid biochemistry, because of their enigmatic properties.

Numerous signaling systems are affected by ceramide. We have manipulated the structure of ceramide at specific sites in order to study how its structure is related to some of its bioactive functions. The accompanying figure illustrates some of the changes we have introduced into the ceramide molecule by chemical synthesis.