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Organisation

Proteinchemistry, proteomics and epigenetic signalling(PPES)

Research Group

Lifecycle:1 Oct 2003 →  Today
Organisation profile:The cluster Proteinscience, proteomics and epigenetic signalling is active on three domains: neurodegeneration, infection and inflammation. For the first part the cluster studies for example the effects of hypoxia/ischemia and the role of hemeproteins herein and how this is perceived in metabolic active tissue such as brain. In the second part the virus-ghost relationship will be studie on intra- and extracellulair level. In the final part the effects of external influences (like endocrine disruptors, hormones, oxidative stress, hypoxia, nutrients,..) will be studied in relation to the protein(signal) function and (epi)genomic regulation of inflammation in immune cells (monocyte, macrophage), cancer cells (CLL, myeloma, breast cancer, neuroblastoma, glioblastoma). All these studies will be performed at the protein, proteome and epigenome level. Following topics will be handled: ¿ Intracellular anti-HIV responses that are mediated by TRIM19 are being studied at the level of protein-protein interactions. A short amino acid sequence is attached to the PML protein, enabling the purification and characterization of PML-associated proteins from virus infected or uninfected cells. Expression and distribution of other anti-HIV proteins such as TRIM5a and APOBEC3G is being studied in immune cells (CD4+, CD8+, monocytes¿) of uninfected, HIV-infected and HIV-resistant individuals (ESN or Exposed Seronegatives). ¿ Extracellular anti-HIV responses. Proteins and peptides of cervico-vaginal washings from healthy individuals are being studied in order to catalogue the many different antimicrobial peptides and proteins that are present in the cervico-gaginal fluid. This work lies the basis for further research on biomarkers for cervix carcinoma (comparison of samples from healthy patients versus samples from precancerous patients). Furthermore, by comparison of cervico-vaginal proteomes from uninfected vs. ESN individuals, we aim to correlate proteome profiles of ESNs and their anti-HIV status. ¿ Proteomics of human adult progenitor cells In collaboration with Regenesys BVBA (Heverlee, Belgium) and Fertipro NV (Beernem, Belgium) we recently started a project wherein growth conditions of human adult progenitor cells (MultiStem®), isolated from human bone marrow, are being studied. In order to meet European guidelines, these cells must be grown in a complete synthetic medium without addition of animal substantia (eg. FCS) as is now the case. Proteomics techniques are therefore applied to identify the secretome of these cells after which growth-promoting and/or differentiating capacities of some characterised proteins on the progenitor cells will be investigated. ¿ Hypoxia/oxidative stress. The effects of hypoxia and the role of hemeproetins herein will be studied in metabolic active tissues such as the brain. The neuroprotective role of neuro- and cytoglobin will be studied in vivo and in vitro using transgenesis (knock-out, overexpressing Mouse models and cellular systems) and differential proteomicanalyses in hypoxia and ischemic mouse models. ¿ Study of the structur/function of globin based oxygensensors. The correct sensing of the oxygen concentration and its changes is of fundamental importance to the cell. One of the potential techniques for oxygen sensing is the use of globin coupled sensors (GCS). Potential oxygen sensors from bacterial systems, Caenorhabditis elegans and vertebrates will be studied at the structural and functional level. The kinetics of ligand binding, conformational changements upon ligand binding, the three dimensional structure and potential binding partners of these sensors will be studied with the goal to perceive a better understanding of this process in the eukaryotic cell.¿ Study of epigenetic programming of inflammation. Controlled inducible expression of inflammation responsive genes is essential during immune responses and immune homeostasis. In contrast, deregulated chronic inflammatory conditions in various cell types frequently result in cancer, cardiovascular or neurological disease. Selectivity, strength and time dependency of gene expression largely depends on activation and interaction of transcription factors/cofactors (i.e. NFkB, AP1, Sp1, HDAC, HMT, SIRT, jmjd HDMT, dnmt, etc.) and their posttranslational modifications with the chromatin environment. Furthermore, chromatin regulation (nucleosome dynamics, histone modifications), noncoding RNAs and epigenetic modifications (DNA methylation of CpG motifs) integrate various input signals (infection, inflammation, stress, metabolism, nutrition) which are ultimately recorded and imprinted into the epigenome. Unraveling the epigenetic interplay of the environment (diet, stress, pathogens, toxins, ...) with the genome in inflammation-cancer models or cardiovascular disease is the major focus of this research topic.Identifying specific protein interactions and signaling functions in relation to epigenetic marks in in different in vitro/ in vivo cell models, representative for cancer, cardiovascular or neuroimmunological disease, is an absolute requirement for translational approaches aiming at identifying small inhibitor molecules (for example derived from medicinal plants) for preventive or therapeutic applications.Our cluster mainly uses proteomics, (epi)genomics and proteinscience technologies. For example we have available a flash-photolyses setup which anables us to determine the ligandbindingkinetics which is unique in Belgium. Specific protein(signaling)functions can be analyzed using different expression- and interactionstudies of recombinant proteins in vitro/in vivo. For the epigenomics studies we will apply new chromatin-proteomic approaches (posttranslational histon/cofactor modifications) and new DNA-methylation-detectionmethods (pyrosequencing, MALDI, AIMS, RLGS, MSPA, bisulfietsequencing)
Keywords:EPIGENETICS, GLOBINS, FUNCTION RELATIONSHIP IN PROTEINS, HYPOXIA, PROTEOMICS, CHROMATIN, PROTEIN-PROTEIN INTERACTIONS, HEMOPROTEINS, INNATE IMMUNITY
Disciplines:Biochemistry and metabolism, Systems biology, Medical biochemistry and metabolism