Raj hooks up with a recently separated woman, Nell, after one of his lectures at the planetarium. Her husband, Oliver, confronts Raj at the planetarium and then breaks down over the end of his marriage. After comforting Oliver, Raj talks to Nell and convinces her to give her husband another chance. Meanwhile, after diving once again into string theory and sprawling his work across his and Amy's apartment, Sheldon approaches a reluctant Leonard and Penny and convinces them to let him use his old room to study for a three-day trial period with an agreement to be quiet and stay out of their way. Sheldon surprisingly sticks to this agreement, being a reasonably good guest, which shockingly frustrates Leonard to no end. After Leonard lets out his frustrations, Sheldon then renegotiates the guest tenancy agreement for an extra few days and resumes being his normal demanding self, much to Leonard's relief.
Star Trek in particular is frequently referenced and Sheldon identifies strongly with the character of Spock, so much so that when he is given a used napkin signed by Leonard Nimoy as a Christmas gift from Penny he is overwhelmed with excitement and gratitude ("I possess the DNA of Leonard Nimoy?!"). Star Trek: The Original Series cast member George Takei has made a cameo, and Leonard Nimoy made a cameo as the voice of Sheldon's vintage Mr. Spock action figure (both cameos were in dream sequences). Star Trek: The Next Generation cast members Brent Spiner and LeVar Burton have had cameos as themselves, while Wil Wheaton has a recurring role as a fictionalized version of himself. Leonard and Sheldon have had conversations in the Klingon language.
Science has also interfered with the characters' romantic lives. Leslie breaks up with Leonard when he sides with Sheldon in his support for string theory rather than loop quantum gravity. When Leonard joins Sheldon, Raj, and Howard on a three-month Arctic research trip, it separates Leonard and Penny at a time when their relationship is budding. When Bernadette takes an interest in Leonard's work, it makes both Penny and Howard envious and results in Howard confronting Leonard, and Penny asking Sheldon to teach her physics. Sheldon and Amy also briefly end their relationship after an argument over which of their fields is superior.
Two physicists from Chicago, Dr. Campbell and Dr. Pemberton, accidentally prove Sheldon and Amy's super-asymmetry theory. This puts them on track for a Nobel Prize, but Leonard points out they tend to go to the experimental scientists who prove a concept instead of theorists like Sheldon who come up with it. Meeting with them, they tell Sheldon they are willing to share the Prize but only three names can be on the submission, and they want to cut Amy out. Amy does not want to prevent Sheldon's lifelong dream, but he goes to President Seibert who agrees to fight for Amy on their behalf. Meanwhile, Bernadette's drug has been approved and she wants to promote Penny to lead the marketing team. Penny resists, knowing Bernadette's attitude at work and doubting her own inexperience to take the responsibility, but Bernadette uses reverse-psychology to get Penny to take the job. Penny mirrors Bernadette's commanding style to get the other employees in line, impressing Bernadette.
Sheldon and Amy are surprised to find that Wil Wheaton's new Professor Proton show is actually very entertaining and that Wil had Howard on as a guest. On Howard's suggestion, Sheldon apologizes to Wil, mending their friendship, and tells him he wants to be on the show; but Wil asks for Amy. Sheldon tells her to do it, but she says she often doesn't do things to avoid upsetting him. Sheldon is horrified when he realises how selfish he has been, especially when he finds out that the men do the same for him. Sheldon encourages Amy to go on the show to inspire girls to pursue science while trying to control his obvious jealousy for her. Meanwhile, Leonard writes a book about a physicist that solves a murder, the protagonist Logan Dean is based on himself. Bernadette points out Logan's mean boss Illsa is similar to Penny, who thinks it is based on Bernadette, though Leonard does not correct her. However, Bernadette tells Penny the truth, upsetting her and making her mad at Leonard. After calling his mother for advice, Leonard learns that Illsa is actually like her; but abandons the book when he realizes he wrote romantic tension into the relationship between the characters.