Intellectual property rights, standards and data exchange in systems biology: Reflections from the IP Expert Meeting at the University of Luxembourg, 8-9 October 2015, ERASysAPP - ERA-Net for Systems Biology Applications.

Intellectual property rights (IPRs) have become a key concern for researchers and industry in basically all high-tech sectors. IPRs regularly figure prominently in scientific journals and at scientific conferences and lead to dedicated workshops to increase the awareness and "IPR savviness" of scientists. In 2015, Biotechnology Journal published a report from an expert meeting on "Synthetic Biology & Intellectual Property Rights" organized by the Danish Agency for Science, Technology and Innovation sponsored by the European Research Area Network (ERA-Net) in Synthetic Biology (ERASynBio), in which we provided a number of recommendations for a variety of stakeholders [1]. The current article offers some deeper reflections about the interface between IPRs, standards and data exchange in systems biology (SysBio) resulting from an Expert Meeting funded by another ERA-Net, ERASysAPP. The meeting brought together experts and stakeholders (e.g. scientists, company representatives, officials from public funding organizations) in SysBio from different European countries. Despite the different profiles of the stakeholders at the meeting and the variety of interests, many concerns and opinions were shared. In case particular views were expressed by a specific type of stakeholder, this will be explicitly mentioned in the text. In this article, we explore a number of particularly relevant issues that were discussed at the meeting and offer some recommendations. SysBio involves the study of biological systems at a so-called systems level. This is not a new concept in the life sciences - many former approaches in physiology, enzymology and other scientific disciplines have already taken a systemic view of selected biological subjects. Yet, SysBio has gained strong interest within the past 10 to 15 years. One predominant reason and a critical prerequisite for this success story being that the relevant scientific methodologies and research tools have become far more powerful and accurate. Remarkable technical progress allows scientists to generate, collect, display and analyse quantitative and qualitative data on biological processes and activities in much greater volumes, velocity, variety and veracity. The skilful integration of multiple heterogeneous data sets allows scientists to model and predict biological processes. SysBio's interdisciplinary nature requires data, models and other research assets to be formatted and described in standard ways to enable exchange and reuse of high quality data [2]. This allows a more effective utilisation of the enormous potential that rests in "big data" analysis. Finally, SysBio is often closely linked to or provides the foundation for Synthetic Biology (SynBio). Standardization and data exchange in SysBio may result in challenges and opportunities related to IPRs. The aim of this article is to raise awareness on these issues within the SysBio scientific community and to stimulate exploration of different strategies for dealing with IPRs in order to optimize access to and use of valuable research results.

Synthetic biology and intellectual property rights: six recommendations.

On 26th November 2013, the Danish Agency for Science, Technology and Innovation organized an expert meeting on "Synthetic Biology & Intellectual Property Rights" in Copenhagen sponsored by the European Research Area Network in Synthetic Biology (ERASynBio). The meeting brought together ten experts from different countries with a variety of professional backgrounds to discuss emerging challenges and opportunities at the interface of synthetic biology and intellectual property rights. The aim of this article is to provide a summary of the major issues and recommendations discussed during the meeting.

Cotranscriptional spliceosome assembly and splicing are independent of the Prp40p WW domain.

Complex cellular functions involve large networks of interactions. Pre-mRNA splicing and transcription are thought to be coupled by the C-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II). In yeast, the U1 snRNP subunit Prp40 was proposed to mediate cotranscriptional recruitment of early splicing factors through binding of its WW domains to the Pol II CTD. Here we investigate the role of Prp40 in splicing with an emphasis on the role of the WW domains, which might confer protein-protein interactions among the splicing and transcriptional machineries. Affinity purification revealed that Prp40 and Snu71 form a stable heterodimer that stably associates with the U1 snRNP only in the presence of Nam8, a known regulator of 5' splice site recognition. However, the Prp40 WW domains were dispensable for yeast viability. In their absence, no defect in splicing in vivo, U1 or U2 snRNP recruitment in vivo, or early splicing complex assembly in vitro was detected. We conclude that the WW domains of Prp40 do not mediate essential coupling between U1 snRNP and Pol II. Instead, delays in cotranscriptional U5 snRNP and Prp19 recruitment and altered spliceosome formation in vitro suggest that Prp40 WW domains assist in late steps of spliceosome assembly.

Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing.

Using the proteomic tandem affinity purification (TAP) method, we have purified the Saccharomyces cerevisie U2 snRNP-associated splicing factors SF3a and SF3b. While SF3a purification revealed only the expected subunits Prp9p, Prp11p and Prp21p, yeast SF3b was found to contain only six subunits, including previously known components (Rse1p, Hsh155p, Cus1p, Hsh49p), the recently identified Rds3p factor and a new small essential protein (Ysf3p) encoded by an unpredicted split ORF in the yeast genome. Surprisingly, Snu17p, the proposed yeast orthologue of the seventh human SF3b subunit, p14, was not found in the yeast complex. TAP purification revealed that Snu17p, together with Bud13p and a newly identified factor, Pml1p/Ylr016c, form a novel trimeric complex. Subunits of this complex were not essential for viability. However, they are required for efficient splicing in vitro and in vivo. Furthermore, inactivation of this complex causes pre-mRNA leakage from the nucleus. The corresponding complex was named pre-mRNA REtention and Splicing (RES). The presence of RES subunit homologues in numerous eukaryotes suggests that its function is evolutionarily conserved.