Maybe not research level.
Let $Z\cong \mathbb{R}$ be the $z$-axis of $\mathbb{R}^3$. Clearly $\pi_1(\mathbb{R}^3-Z)\cong \mathbb{Z}$. Now if $F\subset Z$ is a closed non-empty subset, then one easily sees that $\pi_1(\mathbb{R}^3-(Z-F))=0$.
What is if $F$ is not closed (for example $F=\mathbb{Q}$)?
Is for any nonempty subset $F\subseteq \mathbb{R}$ the space $\mathbb{R}^3-(Z-F)$ simply connected?