Projekt

Combine Model-driven and multivariate analysis to unravel potential therapeutic targets considering inter-tumoral heterogeneity

Udbyder

Vejleder

Sted

København og omegn

Constraint-based analysis of genome-scale metabolic models has become a key methodology to gain insights into functions, capabilities, and properties of cellular metabolism. This systems biology tool has been widely used in cancer research to predict potential vulnerabilities in the metabolic network in the form of synthetic lethal. In brief, synthetic lethals are sets of reactions/genes where only the simultaneous removal of all reactions/genes compromises the viability of the tumoral cell. However, the intertumoral heterogeneity between patients )even with the same cancer type at the same stage) represents an important challenge to be overcame in order to apply these computational approaches in systems medicine approaches.

In addition, since their inception, the size and complexity of genome-scale metabolic reconstructions has significantly increase, thus more computational resources are needed to analyze these systems. This fact is enhanced by the exponential increase of simulations required to unravel potential synthetic lethal genes/reactions as a potential anti-tumoral targets.

Thus, the complexity and size of the metabolic networks together with the large number of simulations needed for synthetic lethal analysis and the inter-tumoral heterogeneity between patients with the same tumor type and stage, make, in practice unfeasible an in-deep study of the mechanisms underlying tumor progression and vulnerabilities via model-driven methods as a translational tool in the scope of systems medicine.

Thus, it is necessary to develop a strategy to reduce the dimensionality of the problem and find more effective ways to develop potential multiple target treatments in complex and multi-factorial diseases such as cancer.

The project: This project is aimed to develop a computational approach combining multi-variate data analysis and model-driven methods that will allow an in-deep discovery of multi-taget metabolic and gene regulatory targets with potential anti-tumoral effects. More specifically it will be achieved by applying three strategies:

  1. Computational metabolic model reduction and compaction

  2. Patients clustering in representative groups based on trascriptomic data

  3. Multivariate analysis in combination with algorithm for the rational reduction of redundant simulations to detect pairs, triplets and quadruplets of genes/reactiosn with anti-tumoral effects

The two first approaches will drastically reduce the number of required simulations while the third will permit to further analyze the behavior of the system.

It is expected that these computational approaches will enable a more in-deep understanding of the complex molecular mechanisms underlying tumor progression and the discovery of novel multi-target therapies towards personalized medicine, that otherwise couldn’t be addressed by current approaches.

This project will be carried out in Prof. Lars Keld Nielsen lab (NNF-CFB DTU, Denmark) and will be under the direct supervision of Dr. Igor Marín.

The role: The successful appointee will apply one or several of the strategies previously mentioned. Finally the results will be analyzed and interpreted in order to describe the mechanisms underlying tumor progression and the discovery of potential novel multi-target therapies.

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)

Forudsætninger

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

Download materiale

Søg i opslag
Kontakt

Virksomhed/organisation

DTU Biosustain

Navn

Igor Batolomé Marín de Mas

Stilling

Co-PI

Mail

igmar@biosustain.dtu.dk

Vejleder-info

Bachelor i General Engineering

Bachelor i Medicin og Teknologi

Bachelor i Bioteknologi

Bachelor i Kemi og Teknologi

Bachelor i Teknisk Biomedicin

Bachelor i Matematik og Teknologi

Bachelor i Kvantitativ Biologi og Sygdomsmodellering

Diplomingeniør, Maskinteknik

Diplomingeniør, Produktion

Diplomingeniør, Eksport og Teknologi

Diplomingeniør, Proces og Innovation

Diplomingeniør, IT-elektronik

Diplomingeniør, Elektrisk energiteknologi

Diplomingeniør, Sundhedsteknologi

Diplomingeniør, Kemi- og Bioteknik (tidl. Kemi- og Bioteknologi)

Sundhedsteknologi

Kemi- og Bioteknologi

Kemi- og Bioteknologi

Kandidatuddannelsen i Kvantitativ Biologi og Sygdomsmodellering

Kandidatuddannelsen i Bioinformatik og Systembiologi

Kandidatuddannelsen i Medicin og Teknologi

Kandidatuddannelsen i Bioteknologi

Kandidatuddannelsen i Kemisk og Biokemisk Teknologi

Kandidatuddannelsen i Miljøteknologi

Kandidatuddannelsen i Matematisk Modellering og Computing

OM DTU

DTU er et teknisk eliteuniversitet med international rækkevidde og standard. Vores mission er at udvikle og nyttiggøre naturvidenskab og teknisk videnskab til gavn for samfundet. 10.000 studerende uddanner sig her til fremtiden, og 5.700 medarbejdere har hver dag fokus på uddannelse, forskning, myndighedsrådgivning og innovation, som bidrager til øget vækst og velfærd.

Find os her

Anker Engelunds Vej 1
Bygning 101A
2800 Kgs. Lyngby


45 25 25 25

dtu@dtu.dk

CVR-nr. 30 06 09 46

Liste over EAN Numre

Job på DTU

Se alle jobs
 

loading..