My Nyblom, Chemical Biology

​​Opponent: Associate Professor Robert Neely, School of Chemistry, University of Birmingham, UK

Supervisor: Professor Fredrik Westerlund, Chalmers
Examiner: Professor Pernilla Wittung Stafshede, Chalmers

Abstract:

The DNA molecule, the blueprint of life, contains an enormous amount of information. The information is coded by the combination of four bases; adenine, cytosine, guanine, and thymine, that, together with the sugar-phosphate backbones, make up the DNA double helix. There are variants in the human DNA sequence that are related to the onset and progression of disease. Under different conditions the DNA can also be damaged, which if not repaired correctly can result in a shortened life span, rapid ageing and development or progression of a variety of diseases, including cancer. Human disease can also be induced by external factors in our surroundings, such as pathogens. One of the cornerstones in modern medicine has been the use of antibiotics to prevent and treat these pathogenic infections, but the global spread of antibiotic resistance is today one of the largest threats to mankind according to the World Health Organization. One consequence of a large global increase in antibiotic resistance would be that routine surgery or chemotherapy treatment might be considered too perilous, because there are no drugs available to prevent or treat the bacterial infections that are closely connected with these procedures.

Novel techniques are needed to characterize different features of DNA in medicine and diagnostics. Single molecule analysis is one method to unveil different kinds of information from individual biomolecules, such as DNA. This thesis uses fluorescence microscopy to shine light upon such information in single DNA molecules from both humans and bacteria, and with that unveil important biological and medical characteristics of that DNA. It describes one method for identifying and quantifying DNA damage induced by a chemotherapy agent, helping to understanding the processes of DNA damage and repair related to diseases and medical treatments. Another method developed is for rapid identification of bacterial infections, with the classification of bacterial sub-species groups and identification of antibiotic resistance genes on plasmids. The methods have the potential to rapidly provide comprehensive diagnostics information, to optimize either early antibiotic treatment or chemotherapy treatment, and thereby enable future precision medicine management.