Abstract: The present invention relates inter alia to methods for identifying modulators of tumour necrosis factor (TNF) signalling. In one aspect, the method involves identifying an agent that modulates a signalling pathway mediated by TNF, comprising the steps of providing a host cell comprising TNF receptor 1 (TNFR1)-associated death domain (TRADD) linked to a reporter molecule, and determining at least one cellular characteristic detectable by the reporter molecule in the host cell in the presence of TNF and in the presence and absence of a candidate modulator. The invention is suitable for high-throughput screening (HTS) and high-content screening (HCS), or a combination of HTS and HCS.