Protein and Structural Biology

Mechanisms and applications of disulfide bond formation

Disulfide bond formation is a complex, essential, multi-factorial process, which is often the rate limiting step in protein folding. Understanding the mechanisms of so-called oxidative folding, allows the generation of new systems by synthetic biology for the efficient production of disulfide bond containing proteins. This allows new structural and functional studies on proteins involved in a very wide range of biological processes and their associated disease states. Current projects are linked to the study of proteins linked to fibrosis and coronary artery disease as well as the generation of novel protein cell factories for protein-based therapeutics and analytics.

https://www.oulu.fi/university/researcher/lloyd-ruddock

Structural and chemical biology of ADP-ribosylation

Human ADP-ribosyltransferases like PARPs catalyze a transfer of ADP-ribose from NAD+ to target proteins and to nucleic acids. The modification serves as a catalyst for recruitment of proteins to e.g. DNA damage site and the signaling event is limited by ADP-ribosylhydrolases. We use structural studies and a range of assay technologies to discover and further develop inhibitors for writers, readers and erasers of ADP-ribosylation. The small molecule inhibitors will serve as tools to study ADP-ribosylation events and also as potential scaffolds for future anti-cancer and anti-viral drugs.

While many structures of individual domains have been elucidated by protein crystallography, we are now reaching towards understanding how the multidomain PARPs function by addressing several key questions in their oligomerization, protein-protein and protein-DNA interactions. We aim to elucidate the structures of these macromolecular complexes at atomic resolution with protein crystallography, cryo-EM and NMR, and complement this with biophysical and biochemical methods.

https://www.oulu.fi/university/researcher/lari-lehtio

Structural Biochemistry: Molecular Machines of Lipid Transport and Metabolism

Lipids are essential constituents of cells and an important source of energy and carbon in living organisms ranging from bacteria to human. A multitude of proteins and enzymes exist in the cell to facilitate the synthesis, transport and degradation of lipids.

Our group’s core interests are to understand the processes of lipid metabolism and lipid transport at a molecular level with a focus on multifunctional enzymes and multi-protein complexes using a variety of biophysical, biochemical and structural biological approaches.

More information here.

In Silico modeling and simulation of biological processes

Computer simulation techniques have become important tools to study the properties of biomolecules and their interactions with other molecules. These techniques are employed with the general objective of predicting and explaining physical quantities and phenomena, such as protein-ligand associations, reaction rate constants of enzyme-catalyzed reactions, acid dissociation constants of proteins, protein domain motion, protein folding and stability, and the like. The underlying computational model provides direct insight into the workings of these molecules, such that statements about their functional properties can be offered. Such knowledge is frequently relied upon, for instance, in the drug design industry to speed up the process of drug finding and drug target analysis. This project is predominantly concerned with the development and application of such techniques.

See also:

https://www.oulu.fi/biocenter/coordinators-projects/juffer

https://www.oulu.fi/biocenter/biocomputing-and-bioinformatics

Structural Biology of the Myelin Membrane

The myelin sheath enables the rapid conduction of nerve impulses in the vertebrate nervous system. The multilayered myelin membrane, tightly wrapped around axons, contains a number of specific proteins involved in myelin formation and neurological diseases. We are interested in the structure-function-dynamics relationships in this unique but diverse set of membrane-associated proteins, in order to better understand the tight packing of the myelin membrane and the factors governing its function in nervous system development, function, and disease. We also use these molecules as general models for protein–membrane interactions. In addition to myelin-specific proteins, we study biomedically relevant protein complexes using state-of-the-art biochemical, biophysical and structural biology methods.

https://www.oulu.fi/university/researcher/petri-kursula

Molecular mechanisms of parasite motility

Our work is aimed at a mechanistic understanding of gliding motility, which malaria parasites and their relatives use for getting to and invading their host cells. We use a broad range of biochemical, biophysical and structural biology methods for creating a complete molecular picture of the parasite actin-myosin motor and the entire glideosome. We also want to understand the evolution of apicomplexan gliding motility and eukaryotic actin-myosin motors in a broader sense. Understanding the mechanistic differences in cell motility between parasites and humans may, furthermore, open up new avenues for treatment and/or prevention of malaria.

More information on research here

Genes responsible for male fertility and Uterine 3D morphology

Our work is aiming to bring new knowledge and deepen current understanding of the fundamental and novel processes related to reproductive biology. We are using mouse and cell culture models to study organogenesis, gene function and signaling. We are having two major focus areas: (i) studies of testes-specific genes’ function and their role in male fertility and (ii) uterine organogenesis and uterine extracellular matrix role in establishment and maintenance of pregnancy. We are using broad spectrum of methods in genetics, molecular biology, biochemistry and employ multiple imaging technologies such as Optical Projection Tomography and Multiphoton microscopy.

https://www.oulu.fi/university/researcher/renata-prunskaite-hyyrylainen