Research

Our group is interested in the application of nanotechnology to biomedicine.  These applications involve the understanding of pain transduction, nanotoxicology, degenerative retinal disease, multiple bimolecular binding and membrane dynamics.  A wide variety of techniques are utilized by our group, which include, fluorescence correlation spectroscopy (FCS) , fluorescence cross correlation spectroscopy (FCCS) , fluorescence confocal microscopy, atomic force microscopy (AFM), dynamic light scattering (DLS), and transmission electron microscopy/scanning electron microscopy (TEM/SEM).

The Cramb Research group

University of Calgary.

Research Projects

It has been shown that up until a certain age, infants have an immunotolerance to foreign blood-type antigens.  In an attempt to induce tolerance to incompatible antigens, A– and B– type antigens are being synthesized and conjugated to silica nanoparticles.  These nanoparticles are characterized by our group in living systems using two photon excitation-FCS.

Nanotoxicology

 

Nanomedicine in organ transplantation

 

Nanoparticles in embryonic models

Nanoparticle toxicology is an increasingly popular and important area of study in adult organisms.  However, the effects of nanoparticles on embryos have not been fully studied. Our group works on injecting fluorescent nanoparticles, such as quantum dots, polystyrene fluospheres and lipid nanoparticles, into chicken embryo models. Our goal is to study potential toxicological effects, such as aggregation and uptake into embryonic blood vessel walls and organs.

Lipid vesicles are attractive drug delivery vehicles in the field of nanomedicine, due to their small size and non-toxic behaviour.  These drug delivery vehicles can be taken up by endocytosis, phagocytosis, or fusion could occur between the liposome and the plasma membrane, releasing the vesicle contents (drug) into the cell.  Utilizing novel fusion agents (general anesthetics) our group aims to better understand the mechanism and kinetics of membrane fusion using steady state fluorescence and FCCS. 

Membrane Dynamics

 

Membrane fusion

 

Three color molecular binding

Fluorescence cross-correlation spectroscopy (FCCS) is a useful technique for detecting association of different fluorescent species in solution.  With increased ability to fluorescently label biomolecules it is now possible to measure interactions critical to specific biological processes.  However, many complex biological pathways involve greater than two simultaneous interactions.  Our group is working towards the direct measurement of  differently colored species using three-color FCCS.

Opioid agonists are the current standard for the treatment of chronic pain. Prolonged exposure to some opioid drugs results in the development of tolerance, whereby the analgesic efficacy of the drug is diminished over time. The cellular and molecular mechanisms that result in tolerance are not fully understood. Our group uses fluorescence spectroscopy to study the interaction between receptor ligands and human m-opioid receptors, which may play a critical role in opioid tolerance development.

 

Human μ-opioid receptor

 

TPE-PDT  for the treatment of degenerative retinal disease

Age-related macular degeneration (AMD) of the eye occurs in a large percent of the population over 60 due to an accumulation of bio-waste and the formation of angiogenic blood vessels in the back of the eye. Together, these cause damage to the macula, and as a result, vision loss. Currently, Verteporfin, in conjunction with laser treatment, is used to treat wet-AMD. Our group uses two-photon excitation to try optimize photodynamic therapy while minimizing damage to surrounding tissue.

Pain Transduction

Photodynamic Therapy

Three-color FCS

Funding