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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 use bioluminescent bacterial strains to develop drug discovery screens. This is achieved by using a battery of bioluminescent bacterial strains and microplate- and array-based formats, 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. For example, we have carried out a screen of 12000 compounds by using the strain E.coli K12/pTetlux, which specifically detects transcriptional and translational inhibitors. In addition, we have also shown the applicability of our approach for natural products by identifying novel antibacterial compounds from fungal extracts and by screening our library of extracts from plants growing in Finland. This research is currently funded by the Academy of Finland (2014-2019)..

We also participated in the FP7-funded Marex (Exploring Marine Resources for Bioactive Compounds: From Discovery to Sustainable Production and Industrial Applications) project. Marex combined 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 collected, isolated and classified 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 were 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 concentrated on screening and characterising the biological activity of samples collected/isolated/synthesised by the other partners. The main focus was on antibacterial and antiviral screening, and on integration of marine-based natural products to the screening. We were also responsible for leading logistics and data management of the project - creating an on-line database for the consortium, which enabled up-to-date data sharing between the partners through a web browser. During Marex ,several active substances were identified and are currently studied further together with the partners. As an example, we have studied bioactive cembrane derivatives from Sinularia kavarattiensis, soft coral collected from the Indian Ocean, in collaboration with National Institute of Oceanography (India), University of Naples (Italy) and EuroEspes Biotechnology (Spain).

Our on-going projects focus on research themes such as biosensor-based HTS and mode of action analysis for enhancing antimicrobial drug discovery against Gram-negative bacteria (funded by Academy of Finland, 2014-2019) and validation of Gram-negative antibacterial targets (INTEGRATE, MSCA-ETN funding for 2015-2019, www.integrate-etn.eu).

Selected Publications:

 

ALL PUBLICATIONS

 

Päivi Tammela, Ph.D., Group Leader

Päivi Tammela received her Ph.D. in Pharmacy in 2004 (University of Helsinki, Finland). Dr. Tammela has served as University Lecturer in Pharmaceutical Biology (2005-2007) at the University of Helsinki; and obtained Adjunct Professorship in Pharmaceutical Biology in 2005. Since 2008, she has served as University Researcher and Group Leader at the CDR where she currently leads the Bioactivity Screening Group. In 2011, Dr. Tammela completed a research visit at the University of Cambridge, Department of Biochemistry, UK. Currently, she holds the Academy of Finland Research Fellow position (2014-2019). Dr. Tammela has authored more than 40 peer-reviewed articles and 7 patents.

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