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Advancement of functional genomics research at the University of Bern by extension of LC-MS platform

English title Advancement of functional genomics research at the University of Bern by extension of LC-MS platform
Applicant Heller Manfred
Number 139231
Funding scheme R'EQUIP
Research institution Department for BioMedical Research Universität Bern
Institution of higher education University of Berne - BE
Main discipline Biochemistry
Start/End 01.07.2012 - 30.06.2013
Approved amount 450'000.00
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All Disciplines (7)

Discipline
Biochemistry
Radiobiology
Physiology : other topics
Immunology, Immunopathology
Nutritional Research, Vitaminology
Experimental Cancer Research
Cellular Biology, Cytology

Keywords (4)

liquid chromatography; mass spectrometry; life science; functional genomics

Lay Summary (English)

Lead
Lay summary
Life science research is performed at many institutes and clinics at the University of Bern and encompasses areas from clinical studies to in vitro experiments involving physiological, pathological and/or cellular model systems. “Omics” technologies are increasingly applied in these projects to gain detailed insights into biomolecular processes involved during homeostasis, regulation and perturbation of biological systems. Although genomics provides useful information on the genetic composition of a cell or organism, it is often insufficient to explain the observed biological phenotypes. These questions need to be answered by studying the entire set of expressed proteins (proteome) as well as the activity state of these proteins and their metabolic products (metabolome). Today, liquid chromatography coupled with mass spectrometry (LC-MS) is the method of choice for the analysis of these biological molecules. The strength of LC-MS lies in the combination of a two dimensional separation of molecules, first in the liquid phase using affinity based resins in a column format (LC), and second in the gas phase (MS) where molecules are separated according to their masses. Chromatographic and mass spectral information is used to identify, characterize and quantify the biological molecules. The University of Bern hosts a large number of research projects funded by the Swiss National Science Foundation that will profit from state of the art LC-MS equipment for analytical purposes. The different projects aim at a better understanding of complex processes involved in initiation and progression of diseases, like inflammation or cancer, as well as of fundamental events underlying basic biological regulations. The acquisition of new LC-MS instrumentation for the Mass Spectrometry Core Facility at the Department of Clinical Research is aimed at improving the support for all those projects.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Collaboration

Group / person Country
Types of collaboration
Interfaculty Bioinformatics Unit of University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Association of Proteomics Core Facilities of Western Switzerland (Repp-So) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Associated projects

Number Title Start Funding scheme
123536 Synthetic Neurochemistry - Introduction of Biophysical Tools into Ion Channels Using Chemical Approaches 01.01.2010 SNSF Professorships
127614 Quality control of gene expression: recognition and elimination of nonsense mRNA 01.10.2009 Project funding (Div. I-III)
124732 Investigation of the induction mechanisms and function of secretory IgA against commensal bacteria using reversible germ-free colonisation 01.04.2009 Project funding (Div. I-III)
130815 Novel biosynthetic pathways in Trypanosoma brucei: Biosynthesis of phospholipids and modification of eEF1A 01.08.2010 Project funding (Div. I-III)
127300 Functional genomics of nutrient transporters in Trypanosoma brucei: From physiology to pharmacology 01.01.2010 Sinergia
125399 Hint1, Hint2, apoptosis and proliferation 01.04.2009 Project funding (Div. I-III)
130780 Studies on the Uncontrolled Proliferation of Theileria-transformed Leukocytes 01.06.2010 Project funding (Div. I-III)
125762 NCCR TransCure: From transport physiology to identification of therapeutic targets (phase I) 01.11.2010 National Centres of Competence in Research (NCCRs)
129706 New approaches in analytical and preparative free fluid electrophoresis 01.04.2010 Project funding (Div. I-III)
135693 In vivo relevance of the PY and PDZ-domain binding motifs of the cardiac sodium channel Nav1.5 01.04.2011 Project funding (Div. I-III)
125150 Structure and supramolecular organization of amino acid and peptide transport proteins 01.05.2009 Project funding (Div. I-III)
132689 Calcium signaling in the heart: Role of SR Ca2+ release channels (RyRs) in health and disease 01.10.2010 Project funding (Div. I-III)
125194 Role of alternative mRNA editing in the developmental regulation of mitochondrial biogenesis in Trypanosoma brucei 01.04.2009 Project funding (Div. I-III)
125394 The link between aberrant MET signaling and DNA repair pathways in liver tumor cells as a target for sensitization to DNA damaging agents 01.01.2010 Project funding (Div. I-III)
117446 Fast, accurate, and sensitive mass spectrometry for basic research in life sciences at the university of bern / mass spectrometer 01.10.2007 R'EQUIP
126020 Regulation of stage-specific gene expression and function of the surface coat of African trypanosomes 01.09.2009 Project funding (Div. I-III)
119984 The role of ABCA1 in the human placenta: physiological relevance and implication in diseases of pregnancy 01.11.2008 Project funding (Div. I-III)
121937 Mitochondrial biogenesis in T. brucei: import of macromolecules and organellar gene expression 01.01.2009 Project funding (Div. I-III)
131038 Synthetic Biology: NANOCELL (09-EuroSYNBIO-FP-012) 01.03.2010 Project funding (special)

Abstract

Life science research is performed at many institutes and clinics at the University of Bern and encompasses areas from clinical studies to in-vitro studies with cellular systems or pathogens. Omics technologies are more and more applied in these projects in order to gain detailed insights into biomolecular processes involved during homeostasis, regulation and perturbation of biological systems. Although genomics provides useful information on the genetic composition of a cell or organism, it is often insufficient to explain the observed biological phenotypes. These questions need to be answered by studying the protein complement (proteome) as well as the activity state of these proteins (metabolome). As outlined in this proposal, the University of Bern hosts a large number of research projects funded by the Swiss National Science Foundation that will profit from a state of the art LC-MS equipment for analytical purposes to characterize, discover and quantify proteins, metabolites and lipids. The different projects aim at a better understanding of complex processes involved in initiation and progression of diseases, like inflammation or cancer, as well as of fundamental events underlying basic biological regulations. For example, plasma membrane embedded channels and transporters are at the top of many intracellular processes. However, this class of proteins is relatively poorly characterized and merits more attention. Furthermore, the metabolome of human blood and urine may reveal changes in the phenotype of cancer under treatment, unravel signaling and metabolic pathways and propose new biomarkers. The same technology will be used in gastro-intestinal research for testing effects of the predominant bacterial metabolites on the host. The metabolomic profiles can then be used to follow medical treatment, leading to a better understanding and improvement of therapy, and for the noninvasive diagnosis of patients with small intestinal bacterial overgrowth. Novel metabolites in body fluids will be characterized to advance drug abuse diagnostics and elucidate biomolecular processes behind drug elimination in humans. Last but not least, lipidomics approaches will be used to characterize lipid biosynthesis pathways in human- and animal-infective parasites, potentially leading to novel approaches to treat diseases.The equipment platform applied for consists of a Qq-Tof and a triple quadrupole mass spectrometer from the same company (e.g. Agilent or Waters). The mass spectrometers will be hyphenated with an ultra performance liquid chromatography system through an electrospray ionization source and nano-flow HPLC through a nano-spray ionization source. Both mass spectrometry companies can provide all instruments and are market leaders in these segments. The Qq-Tof system will serve as a discovery and molecule characterization instrument due to its high resolution (~40’000) and exact mass (<5 ppm) capabilities. The LC and MS equipment from the same provider will allow for easy transfer of scheduled selected reaction monitoring quantification assays onto the triple quadrupole based on the Qq-Tof data. The triple quadrupole instrumentation is of paramount requirement for the molecule quantification work necessary in many of the described projects as well for other services provided to other research groups by the mass spectrometry core facility at the Department of Clinical Research. The total costs of CHF 1’400’000 represent a highly needed investment to continue and increase top quality research in the life sciences at the University of Bern. In addition, this novel mass spectrometry platform will enable project leaders from the University of Bern to attract new collaborations with other Swiss and foreign research groups.
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