Project

Comunity model-driven analysis to unveil metabolic alterations in heterogeneous brain metastasis.

Publisher

Supervisor

Location

Greater Copenhagen area

The major cause of death from cancer is due to metastases that are resistant to therapy. In this sense more than 40% of cancer patients develop brain metastasis (BRM).

The chemotherapy treatment of BRM faces the problem of the impaired delivery of chemotherapy into the CNS due to the impenetrability of the blood–brain barrier (BBB). Additionally, the coexistence within the same tumor of subpopulations, featuring different phenotypes (intra-tumoral heterogeneity) confers an extreme flexibility and adaptability to tumors. Thus, both BBB and intra-tumoral heterogeneity are associated to BRM and represent a challenge for diagnostic and treatment approaches (Renovanz et al Front Oncol 2014).

Therefore, the complex molecular mechanisms occurring in these heterogeneous populations must be approached from a global perspective integrating the whole metabolism and regulatory mechanisms while accounting for intra-tumoral heterogeneity.

In this context, Constraint-based genome-scale metabolic models (GSMMs) have emerged as a potential solution to decipher the complex metabolic mechanisms underlying cancer in a holistic manner (Mardinoglu et al J Intern Med 2012). GSMMs gather all the biochemical reactions encoded by an organism's genome and offers an appropriate framework to integrate a variety of omic data. However, GSMM methods consider tumor as a homogeneous tissue rather than a heterogeneous ecosystem. In this sense mass spectrometry imaging (MSI) techniques may identify intratumoral subpopulations by their unique chemical fingerprints (Palmer et al Anal Chem 2015).

To tackle these biologically and clinically problems, it is imperative to develop novel model-driven methods accounting for tumor heterogeneity to unveil molecular drivers in BRM. It is expected that these computational approaches will enable a more in-deep understanding of the complex molecular mechanisms underlying tumor progression and metastasis associated to brain cancer.

The project: The project is aimed to study the metabolic alterations underlying BRM by developing and applying novel constraint-based methods that consider the tumor as a community of intratumoral subpopulations. To achieve this we will: i) use multivariate approaches to analyze the metabolomic data in order to identify the different intratumoral subpopulations and ii) apply different strategies to integrate transcriptomic, metabolomic and lipidomic data into a computational analysis of the whole metabolism of the different intratumoral subpopulations. This study will provide a holistic view of the molecular processes and mechanisms underlying BRM which ultimately can unveil potential therapeutic targets.

This project is a joint venture between Prof. Lars Keld Nielsen lab (NNF-CFB DTU, Denmark), Prof. Romà Tauler's group (IDAEA-CSIC, Spain) and MD. Algels Sierra‘s group (Clinic Hospital of Barcelona, Spain) that will be under the direct supervision of Dr. Igor Marín.

The role: The successful appointee will apply multivariate analysis to identify the different intratumoral subpopulations and/or a pipeline based on constraint-based methods to integrate and analyze transcriptomic, metabolomic and lipidomic data from the different intratumoral subpopulations. Finally the results will be analyzed and interpreted in order to describe the evolutionary mechanisms underlying the metabolic reprogramming associated to the chronic exposure to EDs in prostate cancer

Criteria: We are seeking for a highly motivated, independent, and well organized person, who is passionate about computational biology. Background on biostatistics and previous knowledge of some programming language (R, Matlab, Python, ...) are desirable but not exclusive.

Those students who are interested in join this project can contact to Igor Marín (igmar@biosustain.dtu.dk

Requirements

We are seeking for a highly motivated, independent, and well organized person, who is passionate about computational biology. Background on bioinformatics

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Contact

Company / Organization

DTU Biosustain

Name

Igor Batolomé Marín de Mas

Position

Co-PI

Mail

igmar@biosustain.dtu.dk

Supervisor info

BSc in Biomedical Engineering

BSc in Biotechnology

BSc in Chemistry and Technology

BSc in Human Life Science Engineering

BSc in Quantitative biology and disease modelling

Bachelor of Engineering

Bachelor of Engineering

Bachelor of Engineering

Bachelor of Engineering

Bachelor of Engineering,

Bachelor of Engineering,

Bachelor of Engineering,

Bachelor of Engineering, Chemical and Bio Engineering (prev. Chemical and Biochemical Engineering)

Health Care Technology

Kemi og Bioteknologi

Kemi- og Bioteknologi

MSc Eng in Quantitative Biology and Disease Modelling

MSc in Bioinformatics and Systems Biology

MSc in Biomedical Engineering

MSc in Biotechnology

MSc in Chemical and Biochemical Engineering

MSc in Mathematical Modelling and Computation

Technical University of Denmark

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