Projects / Programmes
Post-transcriptional regulatory networks in neurodegenerative diseases.
Code |
Science |
Field |
Subfield |
1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
Code |
Science |
Field |
B110 |
Biomedical sciences |
Bioinformatics, medical informatics, biomathematics biometrics |
Code |
Science |
Field |
1.06 |
Natural Sciences |
Biological sciences |
protein-RNA interactions, iCLIP, alternative splicing, 3’ end processing, post-transcriptional regulation, RNA maps, splicing code, high-throughput sequencing, bioinformatics, data mining, data integration
Researchers (20)
no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
1. |
22482 |
MSc Goran Bobojević |
Computer science and informatics |
Researcher |
2014 - 2015 |
12 |
2. |
23399 |
PhD Tomaž Curk |
Computer science and informatics |
Researcher |
2013 - 2016 |
253 |
3. |
16324 |
PhD Janez Demšar |
Computer science and informatics |
Researcher |
2013 - 2016 |
340 |
4. |
32930 |
Aleš Erjavec |
|
Technical associate |
2016 |
12 |
5. |
30697 |
PhD Anja Kovanda |
Neurobiology |
Researcher |
2013 - 2014 |
75 |
6. |
36139 |
Adviti Naik |
Computer science and informatics |
Researcher |
2013 |
0 |
7. |
30710 |
PhD Sonja Prpar Mihevc |
Neurobiology |
Researcher |
2014 - 2016 |
108 |
8. |
30887 |
PhD Anja Pucer Janež |
Pharmacy |
Researcher |
2014 - 2015 |
57 |
9. |
15813 |
PhD Boris Rogelj |
Neurobiology |
Researcher |
2013 - 2016 |
412 |
10. |
33189 |
Anže Starič |
Computer science and informatics |
Junior researcher |
2013 - 2014 |
8 |
11. |
37827 |
PhD Martin Stražar |
Computer science and informatics |
Researcher |
2015 |
35 |
12. |
33328 |
PhD Maja Štalekar |
Biochemistry and molecular biology |
Junior researcher |
2013 - 2014 |
49 |
13. |
30142 |
PhD Marko Toplak |
Computer science and informatics |
Researcher |
2013 - 2016 |
27 |
14. |
34667 |
PhD Jernej Ule |
Biochemistry and molecular biology |
Head |
2013 - 2016 |
179 |
15. |
35506 |
PhD Sabina Vatovec |
Biology |
Researcher |
2014 |
28 |
16. |
37693 |
MSc Maja Vodopivec |
Computer science and informatics |
Researcher |
2014 - 2016 |
3 |
17. |
12536 |
PhD Blaž Zupan |
Computer science and informatics |
Researcher |
2013 - 2016 |
531 |
18. |
30921 |
PhD Lan Žagar |
Computer science and informatics |
Researcher |
2013 - 2014 |
17 |
19. |
32929 |
Jure Žbontar |
Computer science and informatics |
Researcher |
2015 |
9 |
20. |
17285 |
Darja Žunič Kotar |
|
Technical associate |
2013 - 2016 |
2 |
Organisations (2)
Abstract
The recent years have seen an explosion of new methods employing high-throughput sequencing (HTS) to understand the functions of RNA-binding proteins (RBPs). The resulting data requires customized computational tools for its interpretation. Here we propose to develop such tools, with the overarching goal to increase the understanding of the mechanistic principles underlying RNA-dependent regulation of gene expression. Therefore, we aim to drive forward the research in bioinformatics, and provide the tools required by the experimental scientists to study the systems biology of RNA.
The project will develop new data mining and artificial intelligence tools, and embed them into an intelligent web-based assistant for explorative analysis of these data. These tools will significantly advance the data-intensive computational studies of protein-RNA interactions and gene expression. Importantly, these tools will be capable of deriving new hypotheses, which will serve as a starting point for further experiments in the Ule group, aimed at understanding how the defects in the regulatory mechanisms contribute to neurodegenerative diseases. Specifically, we will achieve the following (objectives):
1) Build a computational pipeline to map, quantify and visualize the protein-RNA interactions and model the post-transcriptional regulation of gene expression.
2) Develop a new descriptive language and efficient heuristics to integrate and model the relations among different post-transcriptional regulatory stages and infer new hypotheses explaining the molecular functions of RNA binding proteins and global mechanistic regulatory patterns.
3) Infer predictive models through machine learning and implement an intelligent, web-based interface for explorative analysis that will direct the researcher to the critical regulatory sites and will reveal the regulatory mechanisms unique to each protein.
4) Integrate the data of state-of-the-art high-throughput sequencing methods in order to dissect the molecular mechanisms of the two RBPs associated with neurodegenerative diseases: TDP-43 and FUS.
The Zupan group (FRI), University of Ljubljana, Faculty of Computer and Information Science, Ljubljana, Slovenia has a proven track record in the analysis and visualization of next-generation sequencing data, machine learning and software development. Members of the Zupan group will be working closely together with members of the Ule group (LMB), MRC Laboratory of Molecular Biology, Cambridge, UK, which are developing new experimental methods and have expertise in genomics and studies of protein-RNA interactions. Both groups will collaborate with Rogelj group (IJS), Jožef Stefan Institute, Ljubljana, Slovenia who has expertise in neurobiology and is building resources to study the signaling pathways upstream of the RBPs. The three groups have successfully collaborated in the past and have already produced significant joint research results and publications, which warrant success of the proposed project.
Significance for science
High-throughput sequencing (HTS) allows genome-wide and nucleotide-resolution measurements of the transcriptome and regulation of transcription. A method to study protein-RNA interactions with HTS at high resolution, iCLIP, has been pioneered by our collaborative work. In recent years, iCLIP and related methods have become a central tool for the study of protein-RNA interactions, and are used in hundreds of laboratories around the world. We continue to devise new HTS-based methods, including the proposed pA-seq for the quantification of 3’ end processing. At the same time, HTS-based methods rely heavily on specialized computational tools, which are in great demand and require great effort to design and implement. We have developed such computational tools and provided them as freely available to the research community (https://github.com/tomazc/iCount, https://github.com/mstrazar/iONMF, http://biolab.si/iCLIPro). These tools provide new, very powerful genomic tools for the elucidation of protein-RNA interactions and the advancement of molecular biology.
Significance for the country
The TDP-43 and FUS proteins play an important role in )90% of patients with FTLD or ALS. As such, they are placed at the centre of research into the pathogenesis of these diseases. FTLD accounts for ~10% of all dementia, and ALS is a debilitating motor neuron disease – both diseases have an enormous physical, psychological and economic impact on the community. We have mapped the RNA regulatory networks that are perturbed upon mutations or loss of function of the two proteins. Our results and newly developed computational tools are freely available online to the general research community. A large number of diseases involves defective RNA-binding proteins, but are poorly understood, therefore our tools could enable great progress to understanding fundamental mechanisms of human diseases. The user-friendly database allows experimental scientists to quickly interact with complex data and test new hypotheses. This can be crucial as we move forward to identify the most informative models, which could provide new opportunities for the future studies aimed at the development of new therapeutic strategies. This project importantly improves the efficiency of research in the field of expression regulation. Analysis of HTS (high-throughput sequencing) data is an extremely active field of research in all leading molecular biology laboratories and research universities around the world. With this project, Slovenian researchers have contributed to the development of experimental methods and software tools for HTS, which is increasing the worldwide recognition of Slovenian research excellence and its innovative applications in the field of RNA research. Young scientists and PhD students from UL FRI, UK, and IJS have contribute to the project, which broadened their knowledge and provided opportunities to be involved in cutting-edge, world-class, and high-impact research. PhD students from UL FRI and IJS have been in contact with the Ule group in UK, which has provided invaluable opportunities for students to exchange expertise and design new long-term collaborations. We have promoted the results of our research at international conferences and workshops and have published in leading research journals, which should increase the recognition of Slovenian science. The international research community expressed great interest in our computational tools, which raises an opportunity to develop them further commercially.
Most important scientific results
Annual report
2013,
2014,
2015,
final report
Most important socioeconomically and culturally relevant results
Annual report
2013,
2014,
2015,
final report