Education

BioMedBC stands for Molecular profiling of Bladder Cancer to support personalized medicineand it is a European Project

funded by Marie Sklodowska-Curie Actions.

 

  1. Basics about Marie Sklodowska-Curie Action

Marie Sklodowska-Curie action is a programme that supports the development of scientists at different levels of their career in various research fields. Currently, Marie Sklodowska-Curie action is the main European Union source of founding, taking care of 25.000 PhD students. Among this programme, several funding opportunities exist including Individual Fellowships, Innovative Training Networks, Research and Innovative Staff Exchange and Co-founding of regional, national and international programmes.

 

If you are further interested in Marie Sklodowska-Curie Action, we would like to recommend you to visit the official Webpage: http://ec.europa.eu/research/mariecurieactions/

 

  1. Summary of research cycle

The standard workflow for the scientific research (Figure 1) is originated from the reviewing of existing literature to find and bridge

the gaps in the existing knowledge. Based on above, a scientific hypothesis is generated and a study is designed to prove or not the

hypothesis. While performing a study, a biomarker study in particular, several factors are considered, including:

a) clinical/ disease context,

b) selection of appropriate patients and control groups of individuals,

c) selection of the appropriate statistical and analytical methodologies and

d) selection of the biological material for discovery and intended implementation1.

Followed by the experimental part of the workflow, the findings are evaluated in the biological context and biomarker performance is assessed in a large-scale multi-cohort study in the targeted population2.

 

 

 

  1. Overview on BioMedBC Research

BioMedBC employs  current state-of-the-art proteomics technologies, more knowledge is gained on molecular alterations and mechanisms underlying bladder cancer utilising highly sophisticated Mass Spectrometry-based platforms and systems biology approaches, in order to:

a) collect high dimensional -omics data

b) identify promising protein biomarkers for bladder cancer

c) integrate the new information with the existing knowledge towards molecular characterization of bladder cancer

 

 

Why to study proteins?

Proteomics is the field of science that focuses on the global analysis of protein structures, functions and interactions. Proteins act as catalysts of biological processes and reflect the functional state of the cells. As such, changes at the protein (expression) level are often indicators of disease pathological conditions.

 

  1. Proteomics studies in cancer research

Application of global proteomics analysis in the field of cancer research enable for:

  • better understanding of mechanisms underlying tumorigenesis and/ or associated processes,
  • studying interactions and signaling pathways between cancer and tumor environment,
  • development of molecular signatures for disease,
  • detection of putative targets for drugs,
  • development of clinically useful biomarkers

 

  1. Technological platforms

BioMedBC project combines various research approaches, such as mass spectrometry-based platforms (CE-MS, LC-MS/MS).

 

 

2. Related scientific terms:

 

Proteomic biomarker - Single peptide or protein associated with specific condition, detectable in biological fluids or tissue1.

 

Biomarker profile - Combination of individual peptide/ protein markers by established algorithm providing with the output associated with the specific condition1.

 

MS-based platforms - Mass spectrometry-based analysis enables for detection and quantification of the proteins in the complex biological sample. The high complexity of the human proteome, which is increasing upon trypsin digestion, impose the need for pre-fractionation prior to MS analysis e.g. by using liquid chromatography (LC) or capillary electrophoresis (CE). Since the MS measures the mass over charge ratio of the ions moving in the electric field, in order for peptides to be visible by MS, the ionization is required.

 

CE-MS – MS-based platforms utilized for the analysis of the low molecular weight proteome (peptidome)3. The peptide separation occurs in the capillary according to the charge and size. After the MS analysis, the peptides are defined by the CE migration time, signal intensity and molecular mass. However, CE-MS alone is not applicable for sequencing. CE-MS enables for a fast and reproducible analysis and it has been widely applied for studying the naturally occurring peptides in body fluids.

 

LC-MS/MS – Tandem mass spectrometry combines two mass analysers in one instrument in order to first select the ion from the complex mixture (MS1) and further fragment it (MS2) to obtain the information about the sequence. Fragment masses are used for the database search, when the comparison of theoretical and experimental fragmentation results leads to the peptide identification4. Afterwards, relative quantification may be performed by using spectral counting or intensity-based method.

 

References

 

  1. Mischak, H. et al. Recommendations for biomarker identification and qualification in clinical proteomics. Sci Transl Med 2, 46ps42 (2010).
  2. Frantzi, M., Bhat, A. & Latosinska, A. Clinical proteomic biomarkers: relevant issues on study design & technical considerations in biomarker development. Clin Transl Med 3, 7 (2014).
  3. Stalmach, A., Albalat, A., Mullen, W. & Mischak, H. Recent advances in capillary electrophoresis coupled to mass spectrometry for clinical proteomic applications. Electrophoresis 34, 1452-64 (2013).
  4. Steen, H. & Mann, M. The ABC's (and XYZ's) of peptide sequencing. Nat Rev Mol Cell Biol 5, 699-711 (2004).

 

 
 
 
 
BioMedBC is a Marie Sklodowska Curie Actions (MSCA) Individual Fellowship programme (H2020-MSCA-IF-2016)
funded by the European Union under the Horizon2020 Framework Programme (Grant Agreement:752755) and
coordinated by Mosaiques diagnostics