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Griffiths and Toni Collette were relative unknowns when they were cast as best friends and fellow outcasts in the 1994 film Muriel's Wedding. Her performance won her critical acclaim and both the Australian Film Critics Award and the Australian Film Institute Awards for Best Supporting Actress. She followed this triumph in 1996 with the role of an earthy, ill-mannered pig farmer's wife in Michael Winterbottom's Jude.

Griffiths joined forces again with Muriel director P. J. Hogan for her American film debut, My Best Friend's Wedding, in 1997. That same year she starred in My Son the Fanatic, a British film in which she portrayed a tough Yorkshire prostitute who becomes involved with a considerably older Pakistani taxi driver played by Om Puri.

Griffiths received an Academy Award nomination for Best Supporting Actress for her portrayal of real-life flautist Hilary du Pré opposite Emily Watson as her sister, famed cellist Jacqueline "Jackie" du Pre, in Hilary and Jackie (1998). Showing convincing range, she portrayed Johnny Depp's hysterical mother in 2001's Blow, opposite Ray Liotta.

In 2001, Griffiths was cast as one of the leads in Six Feet Under. Her performance as emotionally-scarred massage therapist Brenda Chenowith earned her Golden Globe and Screen Actors Guild Awards, as well as two Emmy Award nominations. In the third season, the actress missed four episodes due to her pregnancy. By the end of the show's run, she had appeared in almost every episode of the series. At present, she is part of the ensemble cast, co-starring alongside Sally Field and Calista Flockhart, of the dramatic series Brothers & Sisters, in which she portrays Sarah Walker Whedon, who inherits control of the family business after her father's death. Griffiths received a 2007 Emmy nomination for her work on the series.

(wikipedia.org)