Master Thesis Project In Constraint-Based Modeling Of Inborn Errors Of Metabolism

8 Nov 2023

Job Information

Organisation/Company

Université de Lorraine

Research Field

Biological sciences » Other

Researcher Profile

First Stage Researcher (R1)

Country

France

Application Deadline

30 Nov 2023 - 12:00 (Europe/Paris)

Type of Contract

Temporary

Job Status

Full-time

Hours Per Week

38

Offer Starting Date

1 Jan 2024

Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme

Is the Job related to staff position within a Research Infrastructure?

No

Offer Description

We are looking for a candidate for a MSc thesis project with an envisioned length of six months. The project is planned to start in January 2024. It will be carried out at Inserm U1256 NGERE, University of Lorraine, Nancy, France in collaboration with the University Children's Hospital Zurich, University of Zurich, Switzerland.

Constraint-based Reconstruction and Analysis (COBRA) is a widely used systems biology approach to mechanistically model metabolic fluxes on a genome scale. Briefly, COBRA uses molecule-resolved genome-scale reconstructions of a target organism's metabolism to simulate the flow of metabolites in silico. Through integration of meta-omics data such as transcriptomics and proteomics, personalized, sample-and tissue- specific models can be generated and subsequently interrogated through simulations.

Inborn errors of cobalamin metabolism (IECMs) are severe inherited defects in the metabolism of cobalamin (vitamin B12). Cobalamin (Cbl, or vitamin B12) is the cofactor for methionine synthase (MS) and methylmalonyl-CoA mutase (MUT). Inherited errors of Cbl metabolism (IECM) can produce severe manifestations resistant to conventional therapy. IECM result in a range of severe symptoms including metabolic crisis and acute metabolic decompensation suggesting that a wide variety of metabolic pathways are affected. Computational systems biology approaches could be helpful to gain a better understanding of the systems-level abnormalities in metabolism associated with IECM.

In this project, a tissue-specific genome-scale reconstruction of the human fibroblast will be used to model the metabolic states in fibroblasts from patients with inherited disorders of cobalamin metabolism and healthy controls. RNA sequencing data will be retrieved from available cohorts of the cblC, cblG (methionine synthase), and MUT (methylmalonyl-CoA mutase) types of patients and healthy controls. Through integration of omics data, personalized genome-scale models will be created for patients and controls and interrogated in simulations. The aim is to identify metabolic perturbations in patients and gain insight into the variability between patients. Moreover, personalized metabolite supplementations that could partially restore flux through perturbed pathways will be predicted, which could be a first step towards precision medicine interventions in IECMs.

The ideal candidate is a MSc student in bioinformatics, systems biology, or computational biology. Experience in constraint-based modeling would be of advantage. The position is recompensed with a stipend of 500-600€ per month.

Requirements

Research Field

Biological sciences » Other

Education Level

Undergraduate

Languages

ENGLISH

Level

Excellent

Additional Information Work Location(s)

Number of offers available

1

Company/Institute

NGERE Inserm U1256

Country

France

Geofield

Where to apply

E-mail

[email protected]

Contact

City

NANCY cedex

Website

https: // www. univ-lorraine.fr

Street

34, Cours Léopold - CS 25233

Postal Code

54052

STATUS: EXPIRED