Uranium is widely used as an essential fuel source for nuclear fission based reactors. Besides its radioactive properties, uranium is also a toxic heavy metal, which has been unintentionally introduced into aqueous systems, posing contamination issues and is a major concern in remediation strategies. The detection of uranyl(VI) and U(IV) in natural aqueous environments is therefore crucial in deciphering and monitoring its migration behaviour. Chapter two of this thesis focuses on the use of upconversion phosphors (UCPs) to design a sensing system for uranyl(VI). The absorption properties of uranyl(VI) were exploited for resonance energy transfer (RET) with UCPs. Changes in the spectral emission properties, as a result of RET efficiency can be used as a direct measure of the presence of uranyl(VI). This uranyl(VI) sensing system based on UCPs shows proof-of-principle foundations, launching the basis for the development of an indirect system by incorporation of a uranyl(VI) specific ligand, arsenazo III. Chapter three describes the methods employed to target the detection limits of uranyl(VI) sensing from a different approach, with the use of three tryptophan mutants of calmodulin (T34W/T110C, T34CT110W and T34W/T110W CaM). The sensitivity of tryptophan to its local environment allows the monitoring of the fluorescence response as a function of uranyl(VI) and Ca2+ ion binding to CaM. The use of DTPA-bis(TrypOMe) and EDTA-bis(TrypOMe) chelates for the detection of U(VI) and U(IV) ions is described in chapter four. The fluorescence properties of tryptophan were monitored in different buffer systems, with response to the uranium ions. EDTA-bis(TrypOMe) was shown to be a better probe for uranium sensing, attributed to the steric hindrance of full binding to DTPA. Fluorescence responses, as a function of other relevant metals, were also investigated. Finally chapter five outlines the functionalisation of the single tryptophan CaM mutants with CFâ¢350 dye. FRET efficiency between the CFâ¢350 dye and tryptophan was studied to understand the fundamentals of protein dynamics. Consequently, a novel reagent was developed, that showed much promise for the distinguishable detection between uranyl(VI) and Ca2+ with the T34W CaM- CFâ¢350.