Tau is an intrinsically disordered protein found in neurons that binds and stabilizes microtubules. Under pathological conditions, tau aggregates into amyloid fibrils and this process is central to several neurodegenerative diseases, collectively known as tauopathies. It has been proposed that tau pathology occurs in a "prion-like" mechanism, where pathological tau conformers (termed "seeds" or "strains") recruit native monomeric tau to form amyloid aggregates by templated seeding. Recently, a high-resolution clue that distinct tau strains underpin different tauopathies came to light: tau fibrils isolated from tauopathies were found to have distinct core structures by cryo-electron microscopy. These fibril core structures are unique to and homogeneous within one disease, but typically different between different tauopathies. This dissertation is aimed to answer two key questions, which remain unclear in the current state of knowledge: (1) what are the defining properties or conditions that determine the shape of a fibril (e.g. physicochemical conditions, tau state such as mutations, fragmentation, and/or the presence of cofactors)? (2) What structural properties of the fibril are replicated and propagated in seeding, if at all? This work will guide you through a tour to establish the experimental conditions that enable in vitro tau seeding and use these conditions to gain a molecular understanding of tau structures in seeded fibrils.