Research
Research
Graduate Studies
Hepatitis Resources
Viral protein/nucleic acid interactions within the host cell
Proteins (A) and small molecules (B) can interact with G-quadruplexes; capitalizing on key features will enhance selectivity of the agents designed/created.
Targeting the chronic form of Hepatitis B Virus - the cccDNA
Covalently closed circular DNA (cccDNA) hides in the nuclei of infected cells and produces all the transcripts needed for HBV replication. Our current drugs only directly target processes downstream of cccDNA, so if we want to tackle chronic HBV, we first have to find and bind to this form.
We're using structural methods to study the interaction of a host protein with a key site in HBV's cccDNA where it forms a unique DNA structure, a G-quadruplex. Once we know how the host protein attaches, we can determine ways to create a mimetic to bind in a similar way.
Studying the interaction of Hepatitis D proteins with Hepatitis B
HDV is a deficient virus that needs HBV's surface proteins in order to complete its replication cycle. When seen clinically in co-infection, HBV levels are decreased - suppressed by HDV. This project looks at HDV proteins' interaction with HBV RNA to study how it interacts at the molecular level.
Biophysical study of key physiological interactions
PDB from Ladame, et al, 2006; figure adapted from Meier-Stephenson, 2022
Zinc Finger protein interactions with G-quadruplexes
Zinc finger proteins (ZFPs) serve a diverse range of functions in the cell, including DNA recognition and transcriptional activation. ZFPs are also known to bind G-quadruplexes, however there is limited high-resolution data on how this occurs and how this is made selective. This work aims to study the interaction of several ZFPs (Sp1, YY1, MAZ) with promoter-region G-quadruplexes they are known to bind (i.e., c-kit, HRAS, VEGF). Studying and comparing how these interact at the molecular level will provide insights into this class of proteins that play such critical roles in the cell and may provide the template for creating drugs to selectively interfere with these processes.
A Multidisciplinary Team
Our team combines are range of areas of expertise from computational chemistry to biophysics to biochemistry to virology to medicine. Working in a setting where all stages of the discovery process are present and interacting will give a broad scope of the project(s) being worked on.
Collaborators
Here are some of the incredible researchers our team collaborates with:
Dr. Lorne Tyrrell, Distinguished Professor, Dept MMI and Director of Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB
Dr. Kristi Baker, Associate Professor, Division of Oncology, Dept of Medicine, University of Alberta, Edmonton, AB
Dr. David Marchant, Associate Professor, Dept MMI, University of Alberta, Edmonton, AB
Dr. Trushar Patel, Associate Professor, Dept Biochemistry and Chemistry, University of Lethbridge, Lethbridge, AB
Dr. Carla Coffin, Professor and Director of the Calgary Liver Unit, Dept of Medicine, University of Calgary, Calgary, AB
Dr. Julie Lucifora, Researcher, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm, France
Always open to potential collaborations! - please reach out (meierste@ualberta.ca)