Targeted screening technology for identification of bioactive agents with a potential for use in anti-cancer treatment from marine bacteria

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Except for a few examples of successful targeted cancer therapy, commonly used cancer drugs lack selectivity and frequently cause severe side effects. Many anti-cancer drugs induce damage DNA or severely disturb cell cycle regulation as a major part of th eir mode of action. We have recently found a novel PCNA interacting motif, which we have named APIM. The APIM-sequence is identified in over 200 proteins involved in DNA maintenance, epigenetics, cell cycle regulation and transcription. Interestingly, ove r-expression of this motif as well as synthetic APIM-containing peptides, makes cancer cells hypersensitive for different anti-cancer drugs. This is likely due to the APIM-peptides ability to impair DNA repair and cell cycle regulation. In the proposed pr oject we will use human cells expressing the APIM-peptide, relevant chemotherapeutic drugs and advanced robotic culture and sample handling to set up synthetic lethality screens looking for bioactive compounds in extracts from the marine Actinomycete cult ure collection at NTNU/SINTEF.