The Performance: Sarah Polley in ‘Splice’

Sarah Polley had just arrived in Los Angeles after stepping off a plane from her native Canada, but she was already feeling out of place in Hollywood. Late last month, she sat on the patio of a massive hotel suite reserved for Joel Silver, the producer of her new film, “Splice,” gawking at the luxe surroundings.

“Whenever I come to L.A., I always feel like I’m not wearing the right thing or I haven’t got the right haircut or I’m not wearing the right makeup,” she said, looking down at her plain cargo pants and sneakers. “That’s somewhat self-imposed, but it’s also a function of being in a bit of a factory town, where everybody’s thinking about movies all the time and what they look like, and those things never occur to me when I’m home.”

From the beginning of her career, Polley has always been a bit left of center. As a child actress, she made a name for herself playing oddball characters in such films as “The Adventures of Baron Munchausen” and the TV series “Avonlea” and “Ramona.” She cemented her place as an independent film star more than a decade ago in Atom Egoyan’s “The Sweet Hereafter” and later earned a screenwriting Oscar nomination for 2006’s “Away From Her,” which she also directed.

Her latest role is just as characteristically eccentric. In the sci-fi thriller “Splice,” out Friday, Polley stars opposite Adrien Brody as Elsa, a radical scientist who mixes human and animal DNA to create a dangerous new creature named Dren.

“I always assume that I’ll be interested in small independent films, but every now and then, something really surprises me and makes me want to do a bigger film or a genre film,” she said of the script. “This pushed me a little bit. It challenged me and made me feel very uncomfortable at times. I was fascinated by my own response to it, because it really does make you squirm in a deeply uncomfortable, ethical, emotional way that I wasn’t necessarily prepared for.”

To gather a better understanding of the science in the film, Polley spent time trailing a geneticist in a science lab — a dedication that impressed the film’s director, Vincenzo Natali.

“She is the most disciplined actor I’ve ever worked with. She’s obsessed with it,” Natali said. “In order for her to feel comfortable with the technology and the language that was being used, she spent weeks in real labs, so it would become second nature. She rehearsed a great deal. She knew her lines backwards and forward — better than I knew them.”

“What’s wonderful about Sarah is she’s got an eagerness about her,” added Brody. “She’s very collaborative and obviously very intelligent and well spoken, but she has a great sense of humor that comes across in the way she works.”

Polley said she was stirred by the thought-provoking story, which challenged her to question her own beliefs about the morality of tinkering with genetics and “playing God by messing with nature.”

“I’m not a religious person, so, for me, I feel like if [science] can save lives and move us forward, it seems like a really positive thing,” she said. “I think we’re afraid of what science can do and how it can be misused. I see this film as a fairy tale that shows us the absurdity of our fears.”

Though she’s had experience as a director (next month she’ll begin shooting a film she wrote starring Seth Rogen and Michelle Williams), on set, Natali said the actress allowed him to take the reins.

“She was very sensitive to me. She’s a more successful director than me — an Academy Award-nominated writer and, yet, she came only as an actor,” he said. “Even when she isn’t doing much superficially on the screen, you sense there are tremendous things going on under the surface — very deep and tumultuous things. Her acting is very restrained. You’re not ever going to see a hysterical performance from Sarah Polley.”

Her career choices — such as turning down a leading role in Cameron Crowe’s “Almost Famous” — are evidence of her “great intention to avoid mainstream success,” Natali said. “She has chosen the harder road, and she doesn’t care to be famous, which I think means she’s making movies for the right reasons.”

Still, the actress admits she has yet to come to terms with her relationship to acting, even at age 31.

“I think it takes a lot of focus and determination to stay in a relationship with film and acting that’s productive and stimulating,” she said, pushing a strand of her reddish blond hair behind her ear. “Acting can be the most shallow, vapid things you can do with your life, but it can also be one of the most profound experiences in the world. Even my experience acting as a child is something I’m very ambiguous about. I’m not sure it was the best way for me to spend my time. But at the same time, I probably wouldn’t be where I am now without it. And I’m very happy with where I am now.”

amy.kaufman@latimes.com