The Cenozoic is characterized by a change from early Cenozoic greenhouse conditions to the presence of abundant ice sheets in the late Eocene and early Oligocene. As yet, the simulation of this transition remains a challenge and the understanding of trigger mechanisms is limited. In the climate history of the Earth a combination of different processes might have generated climate transitions: Lear et al. (2008) found first proxy evidence for tropical sea-surface-water temperature decrease associated with Antarctic ice growth. DeConto and Pollard (2003) suggested that decreasing atmospheric carbon dioxide might be an important trigger for Antarctic glaciation. Haug and Tiedemann (1998) and Lunt et al. (2008) support the hypothesis that Arctic glaciation was fostered by the closure of the Panama Strait. The PhD project presented here aims to give a more complete mechanistic understanding on how glaciation on Earth occurred. Here we use the comprehensive earth system model COSMOS and a land ice sheet model (SICOPOLIS) to investigate the individual and synergetic contribution of three climate forcings: a) tectonic processes altering ocean gateways; b) draw down of atmospheric carbon dioxide and other greenhouse gases; c) evolution of orbital parameters and subsequent change in radiative forcing. In this presentation we give an overview of the complex experimental set-up, which is applied for long-term transient model runs and discuss preliminary results. First results based on experiments with the ocean general circulation model LSG demonstrate a clear dependence of the advective part of meridional ocean heat transport on the configuration of ocean gateways such as the Panama Strait, the Tethys Seaway and the Drake Passage (Stepanek et al., in preparation). Alteration of ocean gateways therefore might influence glaciation by causing a change in ocean meridional heat transport.