Physics 437: Projects in Biophysics

Home

William R. Bobier
OPT 334 ext. 2090

Development of Ophthalmic Instrumentation in Order to Provide Clinical Measures of the Optical Quality of the Human Eye

Currently we are working with ophthalmic instrumentation which measures the refractive state of the human eye. Light from a collimated IR laser beam is reflected from the eye and returned to the instrument. A waveform analysis is conducted which currently measures defocus. This allows a rapid and objective measure of the eye's refractive error (eg. myopia, hyperopia and astigmatism). By extending this waveform analysis, a wider profile of the eye's optics can be realized so as to include spherical aberration and coma for example.

The current instrument is hand-held and easy to align. By expanding its capacity for optical measures the instrument can have a wider clinical use. One example, would be for the testing of patients who have undergone refractive (laser) surgery to correct their myopia where a wide range of optical changes beyond that of refractive error are needed to be identified.

This project will start by reviewing the instrument's current capacity to measure defocus by reviewing existing images and analyses of subjects with known refractive errors.

Melanie C.W. Campbell
PHY 353 ext. 6273

The Optical Quality of the Human Crystalline Lens and Function of Age
This research is aimed at producing a model of the refractive index distribution within the crystalline lens of the eye which is consistent with measurements of optical properties of the lens. The model would allow the prediction of off-axis optical quality and the variations of the image quality on the retina of the eye with age.

Measuring the Blur of the Image on the Retina of the Eye
Measurements will be made of the optical blur on the retina and its variation with optical correction and with age. A Hartmann-Shack device will be used and calculations made of the aberrations from the images.

High Resolution Ophthalmic Instrumentation Through Improvement of the Image Quality of the Eye
The resolution of instruments used to image structures inside the eye is limited by the blur introduced by the optical component of the eye. A confocal scanning laser microscope (ophthalmoscope) has been constructed in which the eye acts as the objective. The overall resolution will then be improved by correcting the eye's aberrations and reducing the optical blur introduced by the eye. This will be done with a deformable mirror.

Jeff Z.Y. Chen
PHY 355 ext. 5361

Understanding Protein Folding from Polymer Models
The current understanding of the characteristics of protein folding is widely based on statistical-physics models of polymers that capture the essential interactions in real protein systems. The reduction of the degrees of freedom of the involved coordinates in such a model, in comparison with the all-atom modelling approach, allows for accumulation of adequate statistics in computer simulations. This type of models has been successfully used to explore the underlying physical mechanism of structural formation, folding dynamics and protein-protein interaction.

Bae-Yeun Ha
PHY 372 ext. 7004

Understanding DNA: Statics and Dynamics
In addition to carrying life's information, DNA is a fascinating physical object that displays a rich set of conformational and dynamical properties. In aqueous solution, DNA is a highly-charged molecular spring. DNA molecules resist bending, twisting, stretching, and confinement. By themselves, they repel each other but can attract in the presence of polyvalent cations, contrary to our intuition. This project is aimed at developing a theoretical tool to understand physical properties of DNA.

Electrostatics of Biomembranes
Biomembranes are thin lipid bilayers studded with membrane proteins. They are key structural components of living cells: They are not only barriers to the leakage of cell's contents but also serve as binding sites for numerous membrane-binding ligands (e.g., ions and proteins). The objective of this project is to understand the energetics of charged biomembranes interacting with ligands in salty solution.

Stefan Idziak
PHY 250 ext. 5580

Biomembranes
The structure of various novel biomembrane systems will be studied using both in-house and synchrotron x-ray diffraction techniques as well as optical microscopy.

Zoya Leonenko
PHY 354 ext. 38273

Biophysics of lipids and lipid-protein interactions, the role of structural changes and physical properties of lipid monolayers and bilayers in controlling biological processes and diseases, application of lipid films in biomedical nanotechnology.

Methods: Atomic Force Microscopy (AFM), Kelvin Probe Force Microscopy (KPFM), optical/fluorescence microscopy, single molecule force spectroscopy

Current Projects:

  • Amyloid fibril formation and toxicity in relation to Alzheimer’s disease.
  • Development of novel frequency modulation Kelvin probe force microscopy for biological applications.
  • Investigation of structure and function of pulmonary surfactant. Interaction of lung surfactant with nanoparticles, experimental and theoretical.
  • Interaction of antimicrobial peptides with lipid membrane by AFM
  • Applications of lipid membrane in bio-nanosensor development. Development of novel biosensing platforms based on nanoengineered substrates suitable for surface-enhanced spectroscopy.
  • Interaction of magnetic nanopartciles with lipid membrane and cancer cells, collaboration with Prof F.Gu (Chem Eng).
  • Investigating the role of lipid coating and surfactant washing solutions on the physico-chemical properties of lenses, collaboration with Prof L.Jones (Optometry).
  • Development of novel SPM based methods for studying membrane potential and conductance at the nanoscale.
  • EFM and AFM study on organized nanodomains in lipid mixed films for creating nanopatterned surfaces for biotechnology applications.
  • Development of the interface between commercial AFM and mutiprobe micro-chip based SPM, development of biological applications for multiprobe SPM. Collaboration with Prof R.Mansour, El.Comp.Eng.

Qing-Bin Lu
PHY 376 ext. 3503

Our projects are aimed at exploring new exciting frontiers in the interdisciplinary fields of ultrafast biophotonics, femtobiology and femtomedicine, and at establishing an internationally competitive and innovative high-sensitivity femtosecond time-resolved laser spectroscopic laboratory in Canada. The projects will also involve establishing collaborations with other institutions both nationally and internationally and providing training for highly qualified people.

It is anticipated that these projects will involve collaborations with medical biophysicists in the Ontario Cancer Institute at the Princess Margaret Hospital in Toronto and with Prof. Kun Ping Lu's team at Harvard Medical School, Harvard University. There also exists possible collaboration with the pharmaceutical companies like QLT PhotoTherapeutics in Vancouver,BC.

Ultrafast electron transfer reactions in biological systems
Electron transfer reactions are extremely important to our life processes, e.g, during respiration. Our advanced high-sensitivity femtosecond time-resolved laser spectroscopy provides unique capacity to study ultrafast electron transfer reactions that occur in time scales from femtosecond to picosecond in biological systems.

Reaction dynamics of light-activated drugs for cancer therapies
Currently, we are employing unique high-sensitivity and high-resolution time-resolved femtosecond laser spectroscopic techniques for real time studies of reaction dynamics of light-activated drugs. The objective is to obtain real-time observation of light-activated reactions in drugs for cancer therapies including photodynamic therapy (PDT), radiotherapy and their combination with chemotherapy. Efforts are made to identify the molecular pathways that lead to the formation of highly reactive radicals such as singlet oxygen and uracil that then mediate biological effects such as DNA damage and cell death.

Molecular pathways controlling DNA damage and cell death
Recent research indicates that molecular pathways regulated by members of mitogen activated protein kinases and their down stream targets seem to critically modulate cancer cell sensitivity to PDT. Understanding the molecular reactions that contribute to PDT-induced cell death should provide a more rational approach for drug design and therapy. It is expected that some specific molecular groups stimulate the reactions, similar to the processes in UV radiation-induced apoptosis. By using time-resolved femtosecond laser spectroscopy, we are identifying potential molecular reaction pathways that mediate DNA damage and cell death induced by photoactivation of the drugs.

Design of novel near-infrared (NIR) sensitive photodynamic therapy drugs
Once we obtain an accurate understanding of the photochemistry, photobiology and biological effects of light activated drugs, it would be possible to design more effective drugs and to have clinical tests. Specifically we are interested in designing novel NIR single-photon activated drugs for cancer therapy.

Hartwig Peemoeller
PHY 366 ext. 2633

Applications of NMR in Medicine and Biophysics

  • Thermal denaturation of proteins is investigated with 2D NMR and DSC techniques. Improved understanding of the denaturation process and of the denatured material are sought. This research is of fundamental interest and has potential application in cancer therapy.
  • NMR relaxation are studied in articular cartilage tissue and in irradiated polymer gels. The aim is to optimize MRI based joint diagnostics and radiation dosimetry. This research is part of a collaboration with Dr. L.J. Schreiner at the Kingston Regional Cancer Centre and Dr. W. Marshall at Toronto Western Hospital.