Anssi Malinen
Ph.D.
ansmal@utu.fi +358 29 450 4784 Tykistökatu 6 Turku : 6128 |
Biochemistry; enzyme and protein chemistry; enzyme kinetics, enzyme inhibitors molecular biology; mechanism of transcription; ion transporting membrane-bound pyrophosphatases; single molecule biophysics; university teacher
University lecturer 9/2022-
Academy research fellow, group leader 9/2017-8/2022 (5-year term).
Research topic: Regulation of eukaryotic transcription.
Researcher/University teacher at the University of Turku, Department of Biochemistry. 2016-2017.
Research topics: Mechanism of transcription & Molecular evolution of membrane-bound pyrophosphatases.
Postdoctoral fellow at the University of Oxford, Department of Physics. 2014-2016.
Research topic: Single molecule biophysics of bacterial transcription initiation.
Postdoctoral fellow at the University of Turku, Department of Biochemistry. 2009-2014.
Research topics: Mechanism of transcription elongation in bacteria & Mechanism of membrane-bound pyrophosphatases.
Doctoral candidate at the University of Turku, Department of Biochemistry. 2002-2009.
Research topic: Structure and function of membrane-bound pyrophosphatases.
I am interested in the molecular function and regulatory mechanisms of transcription in eukaryotic species. Current projects in my research group revolve around RNA polymerase I (Pol I) that produces ribosomal RNA – building blocks of cell’s protein factories, ribosomes. The synthesis of ribosomal RNA by Pol I accounts for >60% of total transcription in growing eukaryotic cells and constitutes the rate-limiting step of ribosome biogenesis. Oversupply of ribosomes tightly links with accelerated cellular proliferation, while shortage induces cell cycle arrest, senescence or apoptosis in different cell types. To balance the capacity and demand of protein synthesis, many signaling networks that control cell cycle regulate Pol I. Importantly, dysregulation of Pol I activity is linked to the etiology of many human cancers and hereditary disorders.
To understand on the molecular level how the function of RNA polymerase I is regulated in normal and sick cells, we aim to elucidate the identity and sequence of molecular events that take place at the beginning of Pol I mediated production of ribosomal RNA. Our research approach depends on sophisticated biochemical, enzyme kinetic and single-molecule biophysics tools that we develop to monitor the function of Pol I in real-time. The molecular mechanisms that we will uncover pave the way for the development of new drugs that specifically constrain the function of Pol I and hence potentially slow down the progress of cancer and other diseases.
Teaching interests:
Bioprocess technology, mammalian cell factories, enzyme and protein chemistry, transcription, gene regulation, membrane biology.
- Aflatoxin biosynthesis regulators AflR and AflS : DNA binding affinity, stoichiometry, and kinetics (2024)
- Biochemical Journal
- Functional and structural asymmetry suggest a unifying principle for catalysis in membrane-bound pyrophosphatases (2024)
- EMBO Reports
- A methanolic extract of Zanthoxylum bungeanum modulates secondary metabolism regulator genes in Aspergillus flavus and shuts down aflatoxin production (2022)
- Scientific Reports
- Pre-steady-state kinetics and solvent isotope effects support the "billiard-type" transport mechanism in Na+-translocating pyrophosphatase (2022)
- Protein Science
- Quantitative parameters of bacterial RNA polymerase open-complex formation, stabilization and disruption on a consensus promoter (2022)
- Nucleic Acids Research
- Real-Time Single-Molecule Studies of RNA Polymerase–Promoter Open Complex Formation Reveal Substantial Heterogeneity Along the Promoter-Opening Pathway (2022)
- Journal of Molecular Biology
- The Mechanism of Energy Coupling in H+/Na+-Pumping Membrane Pyrophosphatase-Possibilities and Probabilities (2022)
- International Journal of Molecular Sciences
- Catalytic asymmetry in homodimeric h+‐pumping membrane pyrophosphatase demonstrated by non‐hydrolyzable pyrophosphate analogs (2021)
- International Journal of Molecular Sciences
- Good-Practice Non-Radioactive Assays of Inorganic Pyrophosphatase Activities (2021)
- Molecules
- A Single-Molecule View on Cellular and Viral RNA Synthesis (2019) Biophysics of RNA-Protein Interactions: A Mechanistic View Ostrofet Eugen, Stal Papini Flavia, Malinen Anssi M, Dulin David
- Oxazinomycin arrests RNA polymerase at the polythymidine sequences (2019)
- Nucleic Acids Research
- Pausing controls branching between productive and non-productive pathways during initial transcription in bacteria (2018)
- Nature Communications
- Role of the potassium/lysine cationic center in catalysis and functional asymmetry in membrane-bound pyrophosphatases (2018)
- Biochemical Journal
- Two independent evolutionary routes to Na+/H+ cotransport function in membrane pyrophosphatases. (2016)
- Biochemical Journal
- Cytochrome cbb3 of Thioalkalivibrio is a Na+-pumping cytochrome oxidase (2015)
- Proceedings of the National Academy of Sciences of the United States of America
- Evolutionarily divergent, Na+-regulated H+-transporting membrane-bound pyrophosphatases (2015)
- Biochemical Journal
- Monitoring translocation of multisubunit RNA polymerase along the DNA with fluorescent base analogues (2015) Bacterial Transcriptional Control Malinen Anssi M., Turtola Matti, Belogurov Georgiy A.
- CBR antimicrobials alter coupling between the bridge helix and the β subunit in RNA polymerase (2014)
- Nature Communications
- Membrane-integral pyrophosphatase subfamily capable of translocating both Na+ and H+ (2013)
- Proceedings of the National Academy of Sciences of the United States of America
- Membrane Na+-pyrophosphatases Can Transport Protons at Low Sodium Concentrations (2013)
- Journal of Biological Chemistry