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During or following mRNA translation by cytosolic ribosomes the nascent protein being synthesised can be targeted to the endoplasmic reticulum (ER). This targeting of nascent proteins leads to either their transport across the ER or in the case of transmembrane proteins their integration into the ER membrane. This process is carried out by the Sec61 complex which is conserved across organisms including bacteria, yeast and mammals. The ER is a site of protein folding, modification, forward transport and quality control. Misfolded proteins can be directed to the ER associated degradation pathway which mediates retrotranslocation of proteins out of the ER and degradation by the proteasome. A lot is already known about ER associated processes, however, the function of many factors associated with the ER are still poorly understood. Two examples of such factors in yeast include Ysy6p and the ER membrane complex (EMC). The mammalian homolog of Ysy6p, RAMP4 has been shown to be recruited to ribosomes during the integration of transmembrane proteins into the ER and implicated in processes such as protein degradation. The function of the EMC is unknown but has been suggested to function in either protein folding, forward trafficking from the ER or ERAD.Here it has been shown that deletion of EMC1, EMC2, EMC3, EMC6 but not EMC4 or EMC5 causes defects in growth at 39.5°C or on media containing SDS. Defective growth on media containing SDS is suggestive of defects in cell wall or membrane biogenesis and both SDS and elevated temperature are known to cause the induction of the unfolded protein response. This suggests that certain members of the EMC complex are involved in stress responses or secretory processes. Functional investigation of ER associated pathways showed that a ∆emc5 strain has a defect in clearance of the ERAD-M substrate Hmg2-6myc however ∆emc1 does not. The ERAD and competitive growth phenotypes are therefore unlinked and suggests that the EMC complex has a function in multiple pathways which are independently affected by deletion of individual members of the complex. To test whether Ysy6p was a functional yeast homolog of RAMP4, processes previously observed to be involved with the function of RAMP4 were investigated. Strikingly, it has been demonstrated that Ysy6p, similarly to RAMP4, is a protein which tightly associates with ribosomes. In addition, RAMP4 has been previously observed to affect protein degradation whereas here it has been shown that deletion of YSY6 causes an alteration in the degradation profile of Hmg2-6myc. The findings are therefore consistent with the notion that Ysy6p and RAMP4 are functional homologs. In order to further characterise the molecular basis for ribosome association N terminal truncations of opsin tagged Ysy6p were made. It was demonstrated that partial deletion of a conserved cytosolic domain predicted to form a helix-turn-helix resulted in a near loss of cosedimentation of Ysy6p with ribosomes. Furthermore, it was shown that Ysy6p crosslinks with MBS to three factors of 22 kDa, 18 kDa and 10 kDa the identities of which remain undetermined. The data therefore suggest that Ysy6p is involved in processes associated with co-translational integration of proteins and ERAD. In addition, the data also suggest that the EMC complex is involved in ERAD and stress responses.

Catastrophic floods are important events, particularly in the Mediterranean region, where they cause damage to life and property and have major effects on the landscape. Unfortunately, their violence and rarity means that investigating them using conventional hydrological monitoring is often not possible. This study uses palaeoflood hydrological techniques to extend flood records and further our understanding of the occurrence and effects of catastrophic floods in the Mediterranean region. Research has focused on the Voidomatis and Aoos basins; two steepland catchments in northwest Greece. Periods of catastrophic flooding are placed within the context of long-term environmental variability and landscape change, so that the environmental controls on catastrophic flooding, and the effects they have had in the development of these river systems can be fully understood. The late Quaternary behaviour of the Voidomatis River has primarily been controlled by climatic conditions. Uranium-series dating results show that major phases of aggradation took place during the cold stages of the Late Pleistocene. Climatic amelioration in the Lateglacial and the Holocene periods reduced sediment supply and induced progressive incision until the last c. 1000 years or so, when prominent vertical accretion in the contemporary floodplain has occurred. Late Quaternary variations in fine-grained fluvial sediment sources are explored using a quantitative fingerprinting technique. These provenance data are shown to be valuable for reconstructing long-term changes in river activity. Analyses of palaeoflood slackwater deposits provides evidence for the occurrence of two distinct periods of Late Pleistocene catastrophic flooding, at around 21 ka and 17 cal ka. Fine sediment provenance data enable a detailed analysis of catchment conditions at the time of these flood events. Glacial meltwater discharges and general climatic and hydrological instability during the last glacial-interglacial transition were important factors in generating these floods. Palaeoflood information obtained from boulder berms and overbank floodplain sedimentation are combined with the short duration gauged data to develop a record of high magnitude flooding spanning the last 200 years. Catastrophic flooding is shown to reoccur at least every 40 to 50 years. Boulder berms record a decrease in the magnitude of extreme floods over this period, in response to hydrological changes induced by climatic warming following the end of the Little Ice Age (c. 1850 AD). This is one of the first extensive applications of palaeoflood hydrology in the Mediterranean region. High magnitude floods over long timescales are shown to play an important role in the late Quaternary development and contemporary operation of these mountain catchments. This study illustrates the potential value of palaeoflood hydrological techniques to flood prone regions of the Mediterranean, where systematic hydrological data are inadequate for understanding and predicting extreme flood events.