A science teacher at Midtown High, Natalie Osborn has been working on top secret projects for a while. One day, teenager Peter Parker discovers where her projects are hidden and is bitten by one of the genetically altered spiders she created. Peter gains superhuman abilities. However, Natalie has all this time been secretly planning on creating her own super soldier serum.
Throughout the series she is mostly a supporting character and somewhat of a mentor of Peter, helping him in some occasions, until the final season, Season Four. In Season Four, her son Harry returns home after staying with his father for a few years. Harry befriends Peter, and Harry even lets Peter sneak into one of his father's labs. In the lab, Harry is severely injured in a freak accident when he accidentally turns on an unfinished machine that spontaneously combusts.
Enraged, Natalie blames Peter for hurting her son. Natalie finally finishes her super soldier serum and injects into herself so she can personally finish off Peter Parker. However, she is stopped by Spider-Boy and Daredevil. Peter doesn't find out that Natalie is actually the mysterious new villain, who calls herself the "Goblin Queen." Later in the season, when the Carnage symbiote lands on Earth and attaches itself to insane murderer Cletus Kassidy, she witnesses it's destructive power as it nearly kills Spider-Boy. However, Cletus is taken into custody and removed from the symbiote using super sonic soundwaves.
In the series finale, Natalie becomes the Goblin Queen again and forms a team called the Masters of Evil, consisting of infamous super-villains, to break into SHIELD's storage and retrieve the symbiote so she can attach it to herself. However, in the chaos, Kassidy breaks out and reunites with the symbiote. Nick Fury activates the Avengers Initiative to take down Carnage and the Masters. After the battle, Natalie and the Masters are sentenced to life on the R.A.F.T..
- Superhuman Agility - The super soldier serum gave her increased agility and reflexes.
- Claws - The super soldier serum gave her long, sharp claws in place of her finger nails.
- Super Intelligence - Already pretty smart in her normal form, the super soldier serum greatly increased her intelligence.
- Night Vision - The super soldier serum increased her sight and allowed her to see in pitch dark.
- Fangs - The super soldier serum gave her super sharp fangs rather than regular human teeth.
- Superhuman Hearing - The super soldier serum increased her hearing and allowed her to hear things from super far away.