The Allen laboratory contributed important basic research to the development of long-circulating (Stealth) liposomes. Stealth liposomal doxorubicin has received clinical approval. The laboratory's current research in drug delivery is concentrated in ligand-mediated targeting of liposomal anticancer drugs in the treatment of metastic breast cancer and B and T cell malignancies. Basic research into the trafficking of liposomal drugs in cells is also an area of interest. The use of targeted liposomal drugs or liposoma antisense oligonucleotides as a means of overcoming multidrug resistance in cancer cells is another area of interest. Research is also being conducted into targeting non-viral vectors for use in gene therapy.
The primary research focus in the lab is directed toward the structure-function analysis of a new family of viral membrane fusion proteins discovered by my research team. The reovirus fusion-associated small transmembrane (FAST) proteins are the only known examples of membrane fusion proteins encoded by nonenveloped viruses. We believe that the unusual structural and functional properties of the FAST protein family will offer new insights into the mechanisms responsible for protein-mediated membrane fusion, an essential biological process involved in such disparate events as muscle cell differentiation, intracellular vesicle transport, bone development, neurotransmitter exocytosis, embryogenesis, fertilization, and virus-cell interactions. We are also developing a novel fusogenic liposome delivery system based on the FAST proteins. These FAST-liposomes may serve as an improved vehicle for the intracellular delivery of therapeutic drugs, genes, and vaccines.
A second research focus relates to the control of translation initiation in eukaryotic cells. This complex process represents an important step in the overall control of gene expression and cellular function. We are investigating the factors that regulate translation of the unusual polycistronic mRNAs (i.e. mRNAs producing more than one polypeptide) that encode the reovirus FAST proteins.
Throughout his career, Mike Ellison has had a long-standing interest in formalizing biological processes within a predictive theoretical framework. After earning a Ph.D. from the University of Toronto, he spent the next six years at the Massachusetts Institute of Technology developing accurate computational approaches for predicting the physical behaviour of bio-macromolecules. Dr. Ellison moved to the University of Alberta in 1990 where he presently resides as a professor of biochemistry. He has served on the boards of Genome Prairie, the Alberta Network for Proteomic Innovation and founded the Institute for Biomolecular Design that continues to lead in the development of proteomics in Alberta and the evolution of Project CyberCellTM. He is also a co-founder the International E. coli Alliance (IECA), whose mission is to promote and coordinate an international systems biology effort aimed at E. coli an obvious choice as a prototype for whole cell computer modeling.
Recently he has been working toward the establishment of an Albertan program in Synthetic Biology. Synthetic biology attempts to side-step complexity by creating a well-behaved and well-characterized biomolecular parts list, that can be used reliably to build synthetic biological devices. It is a pragmatic understanding of life designed to create living systems with radically different and useful artificial properties.
He has been a pioneer in nanofabrication methods and the application of engineered nanosystems for research and device applications. Throughout his career he has contributed to numerous scientific journals with over 280 published papers. Dr. Craighead¡¯s recent research activity includes the use of nanofabricated devices for biological applications. His research continues to involve the study and development of new methods for nanostructure formation, integrated fluidic/optical devices, nanoelectromechanical systems and single molecule analysis.
Our research centers on the new science and applications of nanometer-scale devices and structures. The behavior of these structures, with dimensions as small as tens of nanometers, can be dominated by effects of size and surface area. Essential areas of study include the development of nanofabrication processes and their impact on the properties of materials and devices.
Our work also focuses on advances in the understanding and manipulation of the physical properties of systems of reduced dimensions. Present research topics include nano-scale analytical systems. We are investigating the application of these advances to the fields of optics and biology.
The main objective is to understand the stability, dynamics, and function of biomolecules and their complexes using computational and theoretical methods, in close collaboration with experimental groups. Major emphasis is placed on the role of water and ions in biomolecular systems, and in particular on hydrophobic and electrostatic effects. Focus areas include theory of single-molecule experiments; channel function; peptide and protein folding; complex formation and ligand binding; proton pumping and bioenergetics; reaction-rate calculations; and the development of new methods for biomolecular simulation and electrostatics.
Research focuses on the development of NMR techniques for studying macromolecular structure and dynamics and the application of NMR techniques to problems of biological and clinical importance. In particular the research is divided into the following areas:
1) Methodological Developments. Research is focused on developing 15N, 13C, 2H multi-dimensional NMR spectroscopy and gradient enhanced spectroscopy to increase the molecular weight limitations currently imposed on protein structure determination using conventional techniques. A second area relates to the development of 15N and 13C relaxation techniques for the study of protein dynamics in solution.
2) Structural Studies of Proteins Involved in Signal Transduction. In particular, we are studying the solution structures of molecules containing SH2 and SH3 domains from cytoplasmic tyrosine kinases. A major goal is to understand in molecular terms the origin of the specificity of particular SH2-phosphotyrosyl peptide interactions.
3) Protein Dynamics. Methods are developed and applied to study backbone and sidechain protein dynamics and how dynamic properties change upon ligand binding or folding. Relationships between dynamics and thermodynamics are being developed and applied to binding and folding events.
4) Protein Folding. Methods are developed and applied to study protein folding, residual structure in unfolded and partially folded states and dynamic properties of these molecules.
Igor L. Medintz studied chemistry and forensic science at John Jay College of Criminal Justice, City University of New York. He received his PhD in 1998 in molecular biology under Prof. Corinne Michels of Queens College (also CUNY). He then carried out postdoctoral research under Prof. Richard A. Mathies in the Chemistry Department of the University of California, Berkeley. This research was focused on the development of fluorescence resonance energy transfer-based genetic assays specifically designed for use on microfabricated bioanalytical devices. He also worked as an analytical toxicologist for three years and in developing drug discovery assays for a pharmaceutical start-up company. Since 2002 he has been at the Center for Bio/Molecular Science and Engineering of the U.S. Naval Research Laboratory, the Navy¡¯s corporate research laboratory, where he is a research biologist. His current research interests include developing facile methods to bridge the inorganic/organic nanoparticle/biological molecule interface in the pursuit of nanosensors and other active nanomaterials in close collaboration with Dr Hedi Mattoussi of the Optical Sciences Division. This work utilizes semiconductor quantum dots as a model nanoparticle. Other areas of interest include understanding the energy transfer interactions of quantum dots and applying them to active biosensing. He has published extensively in different areas including analytical chemistry, forensic science, genetics, nanotechnology, molecular biology and systems biology.