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Bioactivity Screening Group

According to the World Health Organisation (WHO), infectious and parasitic diseases are second among the leading causes of deaths in the world. The need for new antimicrobials has been recognised by the WHO, the European Centre for Disease Control and Prevention, as well as by the European Medicines Agency. The world now faces the challenge of bacteria that are resistant to antimicrobial drugs; especially problematic are the emerging multi-resistant strains. Some examples are vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and Extended Spectrum Beta-Lactamase (ESBL) producing bacteria. Another concern is emerging pathogens, such as viruses, that spread to new areas due to environmental changes. For example, Chikungunya and West Nile viruses are increasingly reported to cause epidemics in Europe and the US.

Novel medicinal lead compounds are sought by assaying large compound collections, which can be generated by combinatorial chemistry or from natural sources. The comparative analysis of synthetic compounds and natural product (NP) pools has shown them to be highly complementary to each other regarding their molecular diversity. Natural products continue to be an important source of novel lead compounds: 34% of new chemical entities introduced as drugs worldwide during 1981-2010 can be traced to, or were inspired by, natural products. Historically NPs have been especially valuable for finding new antimicrobial agents: 47% of new small molecule anti-infective drugs discovered in 1981-2010 are either NPs or directly derived from NPs. However, using natural products in industrial screening campaigns is challenged by the need of screening extract or fraction libraries, and by the fact that the traditional route from the NP to the identification of a purified, active constituent is a laborious and time-consuming process. Our group develops innovative technologies in NP drug screening.

We have developed HTS technologies for discovering antiviral compounds for alphaviruses that manifest themselves as arthropod-borne infections of humans, other mammals, and birds. A collection of pure natural compounds as well as novel, synthetic betulin derivatives (synthesised by Prof. Jari Yli-Kauhaluoma’s group, Division of Pharmaceutical Chemistry) were screened with a reporter gene assay previously developed by us. This screen yielded several hits in low micromolar scale (Pohjala et al. 2009). In 2011, we also described the assay development and screening of inhibitors of alphavirus entry and replication by using a stable Chikungunya replicon cell line and virus-based assays. The main research partners in this work were Doc. Tero Ahola (Animal Virus Group, Institute of Biotechnology) and Prof. Andres Merit (University of Tartu).

We use bioluminescent bacterial strains to develop natural product drug discovery screens. This is achieved by using a battery of bioluminescent bacterial strains that are capable of simultaneously indicating DNA replication or transcriptional inhibition, as well as toxicity of potential antimicrobial samples. Assays are developed into microplate and array-based formats, and further optimised and validated to suit high-throughput screening campaigns. Integration of this methodology for screening of diverse types of samples, especially natural products in conjunction with bioactivity-guided fractionation, is also pursued by screening samples available in our compound and natural product collection. We have carried out a screen of 12000 compounds by using the strain E.coli K12/pTetlux, which specifically detects transcriptional and translational inhibitors (manuscript in preparation). In addition, we have also shown the applicability of our approach for natural products by 1) identifying two novel antibacterial compounds from a fungal extract and 2) screening our library of extracts from plants growing in Finland (two manuscripts under preparation). The main collaborator in this project is Prof. Matti Karp (Tampere University of Technology), who is providing the strains to us. We also participate in the Marex (Exploring Marine Resources for Bioactive Compounds: From Discovery to Sustainable Production and Industrial Applications) EU project. Marex combines the expertise of 19 partners (15 research institutions and four companies) in 13 different countries. Through close co-operation between industrial and academic partners, the consortium collects, isolates and classifies marine organisms, such as micro- and macroalgae, cyanobacteria, sea anemones, tunicates and fish from the Atlantic, Pacific and Indian Oceans as well as from the Mediterranean, Baltic and Arabian Seas. Extracts and purified compounds of these organisms are studied for several therapeutically and industrially significant biological activities, including anticancer, anti-inflammatory, antiviral and anticoagulant activities by applying a wide variety of screening tools. Within the Marex project, our group concentrates on screening and characterising the biological activity of samples collected/isolated/synthesised by the other partners. The main focus is on antibacterial and antiviral screening, and on integration of marine-based natural products to the screening. We are also responsible for leading logistics and data management of the project - creating an on-line database for the consortium, which enables up-to-date data sharing between the partners through a web browser. We have received nearly 700 samples from the partners, and carried out over 2500 experiments. Several active substances have been identified and are currently studied further together with the partners.

We also develop research-based biological and technical understanding and solutions needed for upgrading wood related residues and humic substances to value-added chemicals and materials. This work focuses on wood residues, such as the bark of Betula, Pinus, Picea, Larix, Abies and Populus, as well as on peat, as raw material. These substances represent a rich source of aromatic and other complex structures, which are used as a source for synthetic chemistry. Our group focuses on screening and characterising the biological activity of compounds produced by partners (main collaborators Prof. Jari Yli-Kauhaluoma, Division of Pharmaceutical Chemistry, Prof. Dulcie Mulholland, University of Surrey, and Sami Alakurtti, VTT). The activity of supplied samples against selected microbial strains have been studied, and the most promising compounds were further evaluated through a set of follow-up studies, such as BSA biding, basal cytotoxicity on hepatocytes, and activity in host-pathogen co-culture assays.

The Bioactivity Screening Group actively participates in the Drug Discovery and Chemical Biology (DDCB) consortium within Biocenter Finland (BF), a national infrastructure for drug discovery and chemical biology research in Finland. As a member of BF, they provide contract services and expertise in bioactivity assay development and screening. For more information or to inquire about contract services in these areas, please contact This email address is being protected from spambots. You need JavaScript enabled to view it. .

Selected Publications:


Main instrumentation:

Liquid handling
Biomek FX (BeckmanCoulter)
  • Dual bridge system with 96-channel and Span-8 pods
  • Designed especially for cell-based applications - equipped with shakers, heating blocks, etc.
Nano-Plotter NP 2.1 (GeSiM)
  • Piezoelectric pipetting instrument for sub-microliter dispensing and arraying applications
Varioskan Flash (Thermo Fisher Scientific)
  • Fluorometry, time-resolved fluorometry, photometry, luminometry
  • Variable multi-well plate handling (6 to 1536-well plates)
  • Scanning option, dispensers on board
Victor 2 (PerkinElmer)
  • Fluorometry, time-resolved fluorometry, photometry, luminometry
  • 6 to 1536-well plates
  • 40-plate stackers

Dr. Tammela has served has served as University Researcher and Group Leader at the Centre for Drug Research (CDR) since 2008 where she currently leads the Bioactivity Screening Group.

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