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Supernova chronicles the search and rescue patrol of a medical ship in deep space in the early 22nd century. Its six-member crew includes a Captain and Pilot (Robert Forster), a co-pilot (James Spader), a medical officer (Angela Bassett), a medical technician (Lou Diamond Phillips), a search and rescue paramedic (Robin Tunney), and a computer technician (Wilson Cruz).

When their vessel, the Nightingale 229, answers an emergency distress signal from a comet mining operation in a distant galaxy, the crew soon find themselves in danger from the mysterious young man (Peter Facinelli) they rescued, the alien artifact he's smuggled aboard, and the gravitational pull of a giant star about go supernova - the most massive explosion in the universe.