Grant: Discovery Grants Program - Individual

The unique structure of deoxyribonucleic acid (DNA), which contains the genetic makeup of living organisms, provides a useful template from which to design and build innovative molecules with important applications in science. Indeed, modified DNA pieces have been designed for, and are used in, medicine (drugs that bind to regions in DNA responsible for disease), biotechnology (bioprobes used to study the structure and function of enzymes) and nanotechnology (DNA mediated synthesis of materials and devices on the nanoscale). Despite these useful applications, modified DNA is detrimental when formed within cells, where DNA damage can be formed due to external forces (X-rays, UV light) or internal processes (replication errors, lipid peroxidation) and has been linked to diseases such as cancer. The proposed research uses computational chemistry to study the properties and reactivity of natural and modified DNA components with important roles in biology, biochemistry and medicine. Computational chemistry uses computer calculations to obtain information about chemical systems. Computational chemistry is a useful tool to study modified DNA since calculations can be readily carried out for both normal, stable molecules and reactive species, where experiments on the latter are difficult or impossible. Therefore, calculations can be used to complement and/or guide experiment. Our research will study the chemical removal of damaged DNA that is facilitated by enzymes in our bodies. We will also study the pathways through which the damage forms. By understanding both how nature repairs the damage and how the damage occurs, scientists may be able to develop more effective techniques to repair or prevent DNA damage. We will also study a wide range of chemically modified DNA pieces that have applications as drugs or tools for biotechnology in anticipation to identify new molecules to be made and tested in a traditional experimental laboratory.