Novel methods for selecting signaling aptamers

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Biosensors rely on biomolecules such as proteins and deoxyribonucleic acids (DNAs) for detection. Well-known examples include glucose meters and pregnancy test kits. The former has revolutionized the health care of diabetic patients; and the latter is the current gold standard for diagnosis of pregnancy. Many more people will benefit from biosensors if more diseases or symptoms, such as cancer and heart attack, can be easily diagnosed. Of equal importance is the detection of environmental contaminants. DNA has been known for its function as a genetic material for a long time. Recently, it was discovered that certain sequences of single-stranded DNAs can specifically bind many molecules and these binding DNAs are called DNA aptamers. Compared to antibodies, DNA aptamers have similar or even better binding performance, higher stability and lower cost. Therefore, aptamers are emerging as a new class of reagent for biosensor design. Aptamers are obtained through a selection procedure. Starting with a huge library containing hundreds of trillions of random DNAs, only sequences that can bind target molecules are selected and amplified. Although this method has been successfully applied for aptamer selection, it has several main drawbacks including the needs of linking target molecules to a column and multiple rounds (generally >10) of selection. Currently, only a few high-quality DNA aptamers for small molecules are available. To address these problems, I propose to develop novel aptamer selection methods through DNA library immobilization. Initial targets for selection include disease related hormones, nutrients, and environmental contaminants. A number of highly qualified personnel including graduate and undergraduate students will be trained with this research program. They will be exposed to a highly inter- and multi-disciplinary research environment, learn various molecular biology and analytical chemistry techniques, and develop new nanotechnology-based methods. It is expected that the proposed research will benefit Canada's health care, the environment, and economy.