The human genome contains only ~20.000 genes, however, most of them encode multiple transcripts resulting from alternative promoter usage, splicing, and 3’ end selection. Gene 3’ ends can be defined by the positions of RNA 3’ cleavage, or the location where RNA polymerase II terminates transcription. Alternative 3’ ends determine the properties of the encoded protein: typically its abundance, but sometimes also domain structure – as for immunoglobulin M heavy chain which is membrane-bound or secreted depending on the 3’ cleavage site. Widespread changes in 3’ end usage are characteristic of many processes e.g. differentiation and cancer like neuroblastoma. We do not understand what drives this selectivity. In this research project I will answer the fundamental question of how the location and timing of RNA polymerase II entering into termination mode impacts on the choice of the alternative cleavage and polyadenylation site (Aim 1). I will use biochemical and genetic approaches to elucidate the sequence determinant of alternative cleavage and termination (Aim 2), and investigate sequence-independent components of alternative termination (Aim 3). I recently pioneered the measurement of 3’ cleavage positions together with locations of transcription termination by a novel transcriptomic method. I will apply this method to investigate the timing of changes in cleavage and termination relative to each other on an averaged cell population level, and use a new technique to test this for single molecules. I will also determine the baseline for cleavage site selection utilizing a newly developed in vitro system. Combining those unique integrative and separation-of-function approaches will yield a comprehensive view of alternative gene end regulation. Ultimately, understanding the complex crosstalk between RNA cleavage and transcription termination in alternative 3’ end selection will enable the manipulation of this process e.g. to alleviate diseases such as neuroblastoma.
The objective of the COMPLETE project is to optimize spending of public resources when purchasing network equipment and the related services. As a key approach towards this goal, the project proposes to create a common information platform for public procurers and support them in the procurement process by providing the organizational and technical expertise. Required information under such platform will be gathered from the biggest vendors of optical transport system equipment. Relations with mentioned key vendors need to be established, sustained and promoted. Such platform will significantly improve the quality of decisions taken by public procurers and in some cases would enable to conduct such procurement that previously would not have been possible due to various organizational and technological constraints (for example lack of access to specific technical information and roadmaps). Gathered and sustained information under the platform will be accurate, measurable and comparable as it would be easy for the reader to understand each vendor’s positioning regarding particular technical features. Project will directly coordinate procurement procedures in respect of optical network solutions for the National Research and Education Network environment and public entities. It will support public bodies in procurement procedures and indicate how the procurements can be synchronized with other European Commission programs. Another objective is to define common procurement procedures to help NRENs with the whole process of purchasing new optical networking equipment. There is a number of Horizon 2020 program activities for research, innovation and entrepreneurship that are linked with the project. The results achieved under this project’s proposal will be especially useful for the following two ICT calls: • ICT-27-2015 • ICT-36-2015 • ICT-06-2014