stillingsbetegnelse:
PhD scholarship: Roles of non-histone lysine N-epsilon-acetylation in regulating responses to oxidative stress

jobbeskrivelse:
DTU Systems Biology is seeking a PhD student in collaboration with Nordic Bioscience, for a 3-year project involving characterization of non-histone N-epsilon-acetylation in regulating responses to oxidative stress. Lysine N-epsilon-acetylation is a well-known modification of histones involved in chromatin-based transcriptional control. Recently lysines were found to undergo N-epsilon-acetylation also in extra-nuclear proteins as controlled by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Typically, N-epsilon-acetylation lysine residues are more highly conserved than non-acetylated ones, underscoring their functional importance. Noticeably, lysine N-epsilon-acetylation may be as common as protein phosphorylation and can also modulate phosphorylation-based signalling. Lysine N-epsilon-acetylation was shown in humans, yeast, bacteria and plants, but the impact of these protein modifications is unknown in most cases. Lysine N-epsilon-acetylation probably reflects the acetyl Co-A level and thus the energy balance of the cell. In humans, several N-epsilon-acetylated proteins have been identified which are associated with diseases including heart failure and cancer. Lysine N-epsilon-acetylation was recently found to occur in the endoplasmic reticulum and is potentially a regulator in the protein secretory pathway and unfolded protein response. In addition, the activity of KATs and KDACs is modulated by reactive oxygen species indicating roles of lysine N-epsilon-acetylation in regulating responses towards oxidative stress. Responsibilities and tasks Methods will be established and optimized for enrichment and identification of lysine N-epsilon-acetylated proteins from various biological sources. Peptides and modified lysine residues will be identified using mass spectrometry facilities available at the DTU proteomics platform. Clinically relevant biological samples will be provided by Nordic Bioscience. Lysine N-epsilon-acetylated peptides or proteins with potential as biomarkers for disease will be identified by differential proteome analysis of lysine-acetylation in diseased vs healthy tissue, based on label-based quantification of lysine N-epsilon-acetylated peptides. The mechanisms of acetylation / deacetylation and involved enzymes will be investigated. The role of lysine N-epsilon-acetylation in resistance to ROS will be investigated in various biological systems after inducing stress by treatment with different types of oxidants such hydrogen peroxide and paraquat, and lysine N-epsilon-acetylated peptides will be quantified using isobaric labelling and mass spectrometry. The effect of broad-specificity KDAC inhibitors will be tested and their effect on the lysine N-acetylome will be analysed to provide new information about the downstream targets of these inhibitors. Qualifications Candidates should have a master's degree in molecular biology or engineering or a similar degree with an academic level equivalent to the master's degree in engineering. Approval and Enrolment The scholarships for the PhD degree are subject to academic approval, and the candidates will be enrolled in one of the general degree programmes of DTU. For information about the general requirements for enrolment and the general planning of the scholarship studies, please see the DTU PhD Guide. Assessment The assessment of the applicants will be made by: Professor Birte Svensson and Associate Professor Per Hägglund. We offer We offer an interesting and challenging job in an international environment focusing on education, research, public-sector consultancy and innovation, which contribute to enhancing the economy and improving social welfare. We strive for academic excellence, collegial respect and freedom tempered by responsibility. The Technical University of Denmark (DTU) is a leading technical university in northern Europe and benchmarks with the best universities in the world. Salary and appointment terms The salary and appoin

Arbejdsgiver Navn: Danmarks Tekniske Universitet

Arbejdsgiver telefonnummer: 45252525

Arbejdsgiver faxnummer: 45881799

Job kort beskrivelse:
Undervisning og forskning på universiteter og højere læreranstalter

land: Danmark

region: Hovedstaden

krævede uddannelse: Ikke angivet

Kilde til jobtilbud: AMS, Offentlige arbejdsformidlinger, Danmark