The thesis presents research on human islet amyloid polypeptide (hIAPP) using computational modeling, offering readers a comprehensive introduction to amyloid proteins and the computational methods used with them. Understanding the experimental literature has enabled the critical assessment and comparison of the results to both the literature as well as the experiments performed by collaborators, which further elevates the quality of the research.
hIAPP is related to the development of Diabetes Mellitus type 2, where it forms cytotoxic plaques in the pancreas. It belongs to the amyloid family of diseases, which are characterized by deposits of a particular peptide in the body. The results presented here represent a significant contribution to amyloid research, especially with regard to the origin of cytotoxicity and to developing technologies for early detection. Several studies in the thesis answer difficult questions, which will advance future research into the properties of amyloid proteins. These proteins are highly complex, and the research presented here provides unparalleled insights, revealing in detail the molecular mechanisms behind hIAPP behavior.
Amyloid and Amyloid Fibrils.- Computational Theory.- Imaging Agent Binding to Amyloid Protofibrils.- Determining the Aggregation Prone Structure of hiAPP.- Effect of Terminal Capping on Aggregation of Peptide Fragments.- Coarse Grained Study of Amyloid Protofibril Aggregation.- Conclusion and Perspectives.
Katrine Skeby was accepted into the prestigious honors PhD programme at Aarhus University directly following the completion of her Bachelor's degree in medicinal chemistry. During her PhD studies she has won multiple prizes and grants and has made a significant contribution to the field of amyloid research. Following the completion of her PhD, Katrine was awarded a postdoctoral scholarship from the Carlsberg Foundation to study how molecular dynamics simulations can be used to visualize molecular motion in animation. She is conducting this work at the world-leading scientific animation company, Digizyme Inc., led by Prof. at Harvard Medical School, Gaël McGill.
