Explore the words cloud of the SIRFUNCT project. It provides you a very rough idea of what is the project "SIRFUNCT" about.
The following table provides information about the project.
|Coordinator Country||Denmark [DK]|
|Total cost||1˙758˙742 €|
|EC max contribution||1˙758˙742 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2017-04-01 to 2022-03-31|
Take a look of project's partnership.
|1||KOBENHAVNS UNIVERSITET||DK (KOBENHAVN)||coordinator||1˙758˙742.00|
It was recently realized that lysine acetylation affects a wide variety of cellular processes in addition to the initially recognized histone related gene regulation. Together with recent groundbreaking results, revealing the presence of additional acyllysine modifications, the basis for a paradigm shift in this area was formed. Examples of enzymes formerly thought to be lysine deacetylases, have been shown to cleave these new types of lysine modification and members of the sirtuin class of enzymes play a central role. Development of new tools to investigate the importance of these new modifications as well as the sirtuins that cleave them is required. We therefore propose to adopt an interdisciplinary approach by developing selective inhibitors and so-called activity-based probes (ABPs) and applying these to the investigation of proteins recognizing novel post-translational acylations of lysine residues in cells. Such ABPs will be powerful tools for providing insight regarding this rapidly evolving area of biochemistry; however, the current state-of-the-art in ABP design is endowed with severe limitations because the modifications are inherently cleaved by various hydrolases in human cells. Thus, in the present project, I propose that novel designs accommodating non-cleavable modifications are warranted to maintain structural integrity during experiments. Furthermore, I propose to apply similar mechanism-based designs to develop potent and isoform-selective sirtuin inhibitors, which will serve as chemical probes to investigate links between cancer and metabolism, and may ultimately serve as lead compounds for pre-clinical pharmaceutical development.
AIM-I. (a) Development and (b) application of collections of chemical probes for activity-based investigation of enzymes that interact with post-translationally acylated proteins.
AIM-II. Utilization of structural and mechanistic insight to design potent and selective inhibitors of sirtuin enzymes.
|year||authors and title||journal||last update|
Rajabi, Nima; Svensson, Birte; Olsen, Christian; Olesen, Sita; Madsen, Andreas
An NAD + -dependent sirtuin depropionylase and deacetylase (Sir2La) from the probiotic bacterium Lactobacillus acidophilus NCFM
published pages: , ISSN: 1520-4995, DOI: 10.1101/252379
Nima Rajabi, Marina Auth, Kathrin R. Troelsen, Martin Pannek, Dhaval P. Bhatt, Martin Fontenas, Matthew D. Hirschey, Clemens Steegborn, Andreas S. Madsen, Christian A. Olsen
Mechanism-Based Inhibitors of the Human Sirtuin 5 Deacylase: Structure-Activity Relationship, Biostructural, and Kinetic Insight
published pages: 14836-14841, ISSN: 1433-7851, DOI: 10.1002/anie.201709050
|Angewandte Chemie International Edition 56/47||2019-04-18|
Madsen, Andreas; Olsen, Christian; Moreno-Yruela, Carlos; Galleano, Iacopo
Histone Deacetylase 11 is an Îµ-N-Myristoyllysine Hydrolase
published pages: , ISSN: 2451-9448, DOI: 10.1101/211839
|Cell Chemical Biology 1||2019-04-18|
Are you the coordinator (or a participant) of this project? Plaese send me more information about the "SIRFUNCT" project.
For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.
Send me an email (email@example.com) and I put them in your project's page as son as possible.
Thanks. And then put a link of this page into your project's website.
The information about "SIRFUNCT" are provided by the European Opendata Portal: CORDIS opendata.
A Theory-Oriented Real-Time Operating System for Temporally Sound Cyber-Physical SystemsRead More
Understanding DSB repair from pathway choice to long term effects and their consequences.Read More
Redefining the esophageal stem cell niche – towards targeting of squamous cell carcinomaRead More