Main theme: Quantification of drug-target and drug-off-target binding and understanding the underlying mechanisms.

There are two specific projects currently under investigations: Drug-Lipid binding and Drug-Protein binding

Members in the project: A group consisting of 6 scientists and researchers with Dr. Ashrafuzzaman as Principal Investigator is running these two very big and visionary projects. Among the members there are Biologists, Biochemists, Chemists and Physicists. This has made our research group a vibrant and very diversified one with various available expertise and interests. All the research works are primarily performed in newly created Biophysics Laboratory located in the second floor of Building # 5. Facilities from Protein Research and Genome Research Chairs are also utilized through active collaboration with the members there for better execution of the projects We publish our research achievements regularly in international peer reviewed journals 

Projects for Graduate Students

Our laboratory's ultimate vision is to familiarize various research topics and methodologies among undergraduate and graduate students through proper training. We encourage students to enrich their research skills by working in any of the following projects. Students with interests, passion and enjoyable laboratory works will be able to achieve substantial data and obtain international credentials through publications in peer reviewed journalso Membrane transport phenomena: role of ion channel energeticso Aptamers as theranostic candidates: Implication on Apoptosis in Cancer treatment through regulation of membrane and protein functionso Nanotechnology for drug delivery

Membrane Transport phenomena: role of ion channel energetics

Membrane active agents (MAAs) interact with lipids and change various membrane properties e.g., conductance, lipid phase states, membrane protein structures, etc. Different kinds of ion channels are found to be formed due to different structural complexities of different MAAs like peptides, chemotherapy drugs and possibly many other agents. This project will be dedicated to searching for a possible common mechanism that leads to creating various membrane actions of MAAs. Peptides (gramicidin A, alamethicin, gramicidin S, melittin, etc.), ceramides, chemotherapy drugs (taxol, colchicines, etc.) and aptamers (small DNA oligos) will mainly be used to address the membrane effects.

Aptamers as theranostic candidates: Implication on Apoptosis in Cancer treatment

The project proposes an information-driven approach toward the development of therapeutic drugs targeting apoptosis in cancer treatment. We will target several biomarkers which are known to indicate apoptosis including phosphatidylserine (PS) externalization and we will design and test imaging probes with potential applications in the assessment of patients undergoing cancer treatment. We will also identify potential drug targets to design regulators and test their potency regarding the enhancement of apoptosis in cancer cellsWe consider a set of aptamer based regulators as inhibitors for BCL 2 protein (anti-apoptosis) and enhancers for BAX’s pro-apoptosis effect. We wish to extend our knowledge on the aptamer-protein binding assay by doing some genetic studies in the binding sites 

Nanotechnology for drug delivery

The project proposes a novel nanotechnology based drug delivery protocol targeting cellular interior regions. Treatment of diseases like cancer, Alzheimer’s, neuronal disorders, and many other challenging ones require delivery of drugs near the vicinity of cell membranes or regions beyond where the drugs act on specific proteins, microtubules, nucleic acids, etc. Nanoparticles are popularly used to carry the drugs with them and deliver into the cellular environment. Blood vessels play a major role. Blood fluid carries the nanoparticles with drugs. But the mismatch between required nanoparticle and blood vessel dimensions at cellular environemnt causes lack of successes in delivering drugs beyond cell membranes. It is reported by many investigators that nanoparticle carrying blood vessel’s dimension can not approach as low as even a lipid head group cross sectional area~60 Å2. Transport of nanoparticles beyond membranes therefore requires a very slow and uncontrolled diffusion of nanoparticles across a membrane which is in most cases just unimaginable considering the membrane’s barrier properties. Nanoparticle delivery of drugs beyond cell membrane regions therefore requires a different kind of nanotechnology requiring the consideration of the properties of both nanoparticles and membranes We are in process of developing a novel nanotechnology to solve this issue under this project.

Techniques

Experimental: Electrophysiology recording, calorimetry, circular dichroism, fluorescence measurement, binding assay, capillary electrophoresis, NanoDrop detection of molecules, etcAnalytical and Computational: Thorough analytical and numerical analysis of the biological problems and related in silico studies/experiments using molecular dynamics simulation. Mathematica and other necessary programs will be used to parameterize the problems.

Collaborators

Kingdom of Saudi Arabia, Riyadh-King Saud University
  Dr. Abdulrahman M. Alsenaidy
  Dr. Mohammed S. Alanazi
  Dr. Zahid Khan
  Dr. Mohammad Ayoub Akli

Canada, Edmonton, Alberta-University of Alberta
 Dr. Jack Tuszynski
 Dr. Richard Tseng
 Dr. John Mercer

USA, New York-University of Cornell
 Dr. Olaf Sparre Andersen
USA, Maryland-University of Maryland
 Dr. Marco Colombini