An accidental discovery: From failed experiment to new antibiotic

NTNU professor Marit Otterlei nearly threw out the contaminated cell culture where she and her colleagues were testing a new cancer drug.

The problem arose on a hot summer day, in Trondheim, in a country not known for hot summer days. So they'd opened the lab's windows overnight.

When they came back the next day, they found an uninvited guest, snuggled in with their cancer cell culture: Bacteria!!!

Here's the thing, though: although the drug had been designed to work on human cancer cells, it looked like it had killed the bacteria, too!

That was remarkable, because the cancer drug targeted a specific mechanism that human cells use to replicate. It looked like the drug also targeted the same mechanism in bacteria -- even though the tree of life had branched away from bacteria 3 BILLION years ago! How could that be?

Today's podcast takes a peek into the challenging world of what it takes to bring a drug, especially an antibiotic, to market. But it’s also an inside look into how some researchers, with their deep curiosity about the nuts and bolts of how life actually works, can come up with startling discoveries that may someday save our lives. Sometimes, the key to saving lives can be hidden in a protein that hasn't changed much over billions of years.

Our guests on today's show are Marit Otterlei, a professor at NTNU's Department of Clinical and Molecular Medicine; Siril Skaret Bakke, innovation manager at NTNU's Technology Transfer Office AS, and Christine Årdal , senior researcher at the Norwegian Institute of Public Health.

Marit is a part-time CSO at APIM Therapeutics (https://www.apimtherapeutics.com/), which is developing the cancer drug that she was testing back in 2011, when an open window on a hot summer day led her to suspect that her substance might a possible antibiotic, too. That antibiotic, Betatide, is now undergoing testing that pharmaceutical companies require before investing in it.

Here's a list of some of the key academic publications:

Gilljam, Karin Margaretha; Feyzi, Emadoldin; Aas, Per Arne; Sousa, Mirta; Müller, Rebekka; Vågbø, Cathrine Broberg. (2009) Identification of a novel, widespread, and functionally important PCNA-binding motif. Journal of Cell Biology

Nedal, Aina; Ræder, Synnøve Brandt; Dalhus, Bjørn; Helgesen, Emily; Forstrøm, Rune Johansen; Lindland, Kim. (2020) Peptides containing the PCNA interacting motif APIM bind to the beta-clamp and inhibit bacterial growth and mutagenesis. Nucleic Acids Research (NAR)

Nepal, Anala; Ræder, Synnøve Brandt; Søgaard, Caroline Krogh; Haugan, Maria Schei; Otterlei, Marit. (2021) Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization. Frontiers in Microbiology

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