A mathematical approach using fractals is being employed to model analyte-receptor interactions on biosensor and other surfaces. Fractals are self-similar disordered systems and this disorder is described by non-integral dimensions. We will be making quantitative the heterogeneity, or surface roughness by using the fractal dimension, or the Df value. Kinetic parameters like binding and dissociation rate coefficients will be calculated. We will then attempt to link and study the effect of the surface heterogeneity on these parameters.
The SPR biosensor is gaining widespread importance as a bioanalytical tool in the pharmaceutical and biotechnology industries. We have obtained analyte-receptor (antigen-antibody) binding data from the literature and modeled it using the above approach. Heterogeneity on the SPR biosensor mainly arises due to (i) the nature of the chip surface, (ii) nature of the ligand, and (iii) immobilization of the ligand and the immobilizing conditions. Fractal dimensions and binding and dissociation rate coefficients are calculated and linked to experimental parameters like analyte concentration, pH etc. The analysis will help in better understanding of analyte-receptor interactions occurring on biosensor surfaces and will provide further physical insights into these reactions. We are hoping to make recommendations which will help in better design of biosensors, and also improve the speed, sensitivity and specificity of existing biosensors; this is the ultimate goal of the project.
This is a joint research effort with the departments of Pharmacology, Pharmacognosy, and Biology at Ole Miss; the University of Mississippi Medical Center; and Xavier and Tulane Universities, as a part of the UM Congressional Initiative. The research effort at Ole Miss is mainly directed towards studying the steroidogenic effects of contaminants in the Mississippi River Basin on fishes and humans (mainly pregnant women). Using our analysis we are determining the kinetic parameters for the binding of estrogens and other chemicals to ER receptors and how they can be modulated to alleviate some of the deleterious effects of these compounds. The analysis will provide some insight into the reactions modulated by these nuclear receptors. This might help in better understanding of the serious diseases (for example, breast cancers) which may be caused by these hormonal imbalances.
In DNA hybridization reactions there is base pairing of two single stranded (ssDNA) molecules to form double stranded DNA on biosensor surfaces. This is particularly important as knowledge of the kinetics of this association will provide insights which might be useful in investigating single point mutations and base pair mismatches which have been implicated in serious diseases like Multiple Sclerosis, etc.
The fractal technique is being employed to study the binding of cells to receptors, proteins and other cells immobilized on biosensor surfaces and in the body. This can provide valuable insights into the mechanisms of many diseases, and lead to design of vaccines and drugs which can modulate or decrease the binding of microbial cells to body receptors and thereby prevent infections.
The main goal of this project is to analyze biomedical signals like ECGs and EEGs using commercial Fractal Vision 4.0 software. We are determining fractal dimension values for these signals under different conditions. By comparing the values of the fractal dimension values under different conditions we may be able predict the onset of a pathological condition. The ECGs are obtained from literature or from actual clinical surroundings. We have used the analysis for risk-stratifying closely related family members for the presence of serious genetic heart diseases. We have done the risk-stratification analysis for families suffering from a very serious disease called Hypertrophic Cardiomyopathy. Attempts are also being made to extend the analysis to include more families and also screen other diseases. Finally, we would also like to incorporate this procedure online so as to allow for continuous monitoring of an individual's heart condition.
Protein folding, whereby the protein acquires its native and active structure starting from a linear inactive state, is a central problem in biology. Our aim is to review and classify protein folding and misfolding mechanisms. Protein misfolding has been implicated in many serious illnesses like Alzheimer's and Arthritis. The key to discovering many therapies may be linked to correct protein folding.Our aim is to understand why proteins misfold and how they may be induced to fold properly.
Anand Ramakrishnan is a 5th year PhD student from Mumbai, India. He is currently working on using fractal models to analyze Analye-Receptor interactions on biosensor and other surfaces. He has also had hands-on experience, having worked with the BIAcore biosensor (SPR biosensor) during his summer internships with Connex GmbH, Martinsried, Germany and Pharmacia Corporation, Chicago, IL. Anand is also interested in extending the fractal approach to biomedical applications. For more details, email Anand or view Anand's resume.
Harshala Butala is a first year MS student from Pune, India. Harshala has started research work on the Congressional Initiative project to study the steroidogenic activity of chemicals on fishes in the Mississippi River basin. Harshala is a part time research assistant in the Department of Pharmacology where she is studying the metabolism of estrogens derived from fishes, using Gas chromatographic techniques. For more information, email Harshala.
Nigil Satish is a first year MS student from Chennai, India. Nigil's thesis deals with kinetic mechanisms of protein folding and misfolding and their biomedical implications. Nigil is a research assistant with the Department of Pharmacognosy, where he is involved in the extraction of sesquiterpene lactones from medicinal plants (magnolias) to find antimalarial and antitubercular activity, isolation of sesquiterpene lactones using HPLC, and efforts to determine its structure using NMR spectroscopy. For more information, email Nigil.
|
|
|
