Current research in Biochemistry
Biochemistry is the study of the chemical processes in living organisms. Modern biochemistry tries to answer questions that are related, for example, to the regulation of gene expression or the structure and function of cellular proteins. The research performed by the Biochemistry division in the University of Turku is focused on the structural and functional analysis of mammalian and bacterial proteins, enzymology, microbial molecular biology and immunochemistry.
Research Projects
Aa-group:Biofilm-host Interaction in Chronic Infection
Biofilms, bacterial communities surrounded by protecting extracellular matrix, are resistant to antibiotics and the host defense systems. Most recent research results suggest that the inter-kingdom signaling between biofilm forming bacteria and the host cells might elucidate the different phases in chronic biofilm infection. The aim of our studies is to illuminate the molecular mechanisms of biofilm-host crosstalk in aggressive periodontitis, a chronic infection destroying the tooth supportive tissues.
Lysosomal proteins
Lysosomes have important role in cell defence and recycling of molecules. The lysosomal hydrolases cleave proteins, lipids and carbohydrates. Mutations in these enzymes or in proteins involved in recognition and transport of lysosomal proteins cause severe Lysosomal Storage Disorders (LSDs). Our overall aim of is to increase the structural knowledge of the lumenal lysosomal proteins and their transport by combining X-ray crystallography, structural and proteomic analysis, and cell biology.
Antibiotic Biosynthetic Enzymes (ABE)
Our research is focused on the chemical biology of bioactive secondary metabolites produced by different members of the bacterial genus Streptomyces. We study the biosynthetic reactions of aromatic polyketide compounds, a diverse group of metabolites used widely in medicine, agriculture and other fields of commerce. Central areas of our research involve molecular genetics, in vivo analytics, combined in vitro enzyme chemistry and structural biology, and natural product chemistry of the biosynthetic pathways. Project Leaders: Jarmo Niemi / Pekka Mäntsälä / Mikko Metsä-Ketelä
Cell Adhesion and Cancer
Cancer progression involves uncontrolled proliferation and motility of cells. Integrins, transmembrane cell surface adhesion receptors, are proteins known to regulate cell behaviour by transducing extracellular signals to cytoplasmic protein complexes. We have performed genome-wide screens to identify integrin-binding intracellular proteins and demonstrated that recruitment of specific protein complexes by the cytoplasmic domains of integrins is important in tumorigenesis. Our aim is to extend our studies on the novel integrin binding proteins to gain insight on the diverse biological roles of integrins in cancer.
Immunochemistry
Our environment contains a great variety of infectious microbes –viruses, bacteria, fungi, protozoa and multicellular parasites. These can cause disease, and if they multiply unchecked they will eventually kill their host. Most infections in normal individuals are short-lived and leave little permanent damage. This is due to the immune system, which combats infectious agents. Since micro-organisms come in many different forms a wide variety of immune responses are required to deal with each type of infection. On the other hand, there are many beneficial commensal micro-organisms, which compete effectively with many potential pathogens.
Structure and Function of Collagen Receptor Integrins
Integrins are signaling transmembrane cell adhesion receptors that connect the cell to the extracellular matrix composed of collagen and other matrix molecules. Integrins play crucial roles in growth, development, migration, defense mechanisms and apoptosis of the cell. We are focused on the collagen receptor integrins. Small molecule drugs targeted to these integrins could be used to cure cancers, inflammations, and cardiovascular diseases. We are currently elucidating the activation mechanism of the collagen receptor integrins and its influence to intracellular signaling. We are also studying integrin internalization from the plasma membrane. In addition to common methods in molecular, structural and cell biology, we use combined atomic force/confocal microscopy and proteomics in our research.
Mechanistic Enzymology of Inorganic polyphosphatases (POP)
We are carrying out molecular biological, functional and structural studies of enzymes involved in the metabolism of inorganic polyphosphates, which are vital cellular high-energy compounds and regulators. The simplest polyphosphate, pyrophosphate (PPi), provides the thermodynamic driving force for biosynthetic reactions, such as protein, RNA, and DNA synthesis, whereas polyphosphates (polyPs) are involved in blood clotting, mammary cell proliferation, inflammation, and metastasis in animals.
RNA polymerase and Mechanism of Transcription
RNA polymerase is the enzyme that carries out the first step in gene expression, synthesis of RNA. We study RNA polymerase catalytic mechanism with emphasis on translocation, a step specific to processive polymerases and motor enzymes.