Postdoctoral Researcher

Malignant hyperthermia (MH) is a dangerous reaction to certain anesthetics, heat or exercise that can be fatal if left untreated, caused by an inherited dysregulation of calcium inside muscle cells. MH can be prevented by using alternative anesthetics in patients with suspected MH predisposition and in their relatives. At least half of the families affected by MH predisposition have no identifiable genetic marker and cannot benefit from genetic testing.

We envisage developing a test to diagnose MH using a harmless acupuncture needle applied into muscle. Needles for this “chemical biopsy” are coated with a sorbent designed to extract specific molecules (i.e., biomarkers) by a process called solid phase microextraction. A microinjection of caffeine into the muscle would trigger a local reaction only in patients predisposed to MH — but not in others, producing biomarkers that can be extracted by the modified needle and analyzed for diagnosis. USP is part of a multidisciplinary international consortium with the expertise to develop such a device and to test its diagnostic accuracy in a multicenter clinical trial.

Qualification/Background required:

- PhD, knowledge of LC-MS y sample processing technologies.
- Valuable training: Statistics. Metabolomics.
- English C1 level

Experience and requirements:
Analytical laboratory research experience.

Postdoctoral Fellow with knowledge in both untargeted and targeted metabolomics analysis with LC-QTOF-MS and LC-QQQ-MS; metabolite identification; multivariate data analysis and pathway analysis.

She/he will collaborate with CEMBIO researchers and bioinformatics involved in the project and with the International Partners from Canada, Austria, Poland, Switzerland and Turkey.

Roles and responsibilities of the position:
Discovering and validating biomarkers using metabolomics in muscle samples from MH-susceptible patients. We will carry out untargeted metabolomics analyses using a set of muscle samples from MH-susceptible and control patients. We will search for biomarkers that (a) differ between MH-susceptible and MH-negative patients at baseline (i.e., before pharmacological challenge), and (b) show significant differences between MH-susceptible and MH-negative patients in terms of fold-changes from baseline in response to caffeine and halothane. Metabolomic coverage will be based on quadruple time-of-flight mass spectrometry tools. In order to expand coverage and achieve higher yield metabolite identification, reversed-phase liquid chromatography - mass spectrometry will be used for lipidomics analysis, while hydrophilic interaction liquid chromatography - mass spectrometry will be used to analyze polar compounds in both positive and negative ionization modes.

Data from the multi-platform analysis will be extracted and filtered out. Different tools will facilitate this process: CEU Mass Mediator; Lipid Annotator and in-house libraries.

After defining the metabolic signatures of MH susceptibility, we will develop targeted analytical methods based on liquid chromatography triple quadrupole tandem mass spectrometry, to improve the selectivity and sensitivity of the further quantitative analyses. The selected compounds will be validated as biomarkers using receiver operating characteristic curve analysis. In addition to their diagnostic value, we expect that discovering the altered biochemical routes underlying MH susceptibility will provide further biological understanding of this rare disease.

Finally, we will validate the biomarker profiles in a new sample of MH-susceptible and control patients from Toronto’s MH Biobank and, if necessary, collaborating MH testing centres across Europe. We will also work in optimizing SPME - mass spectrometry in muscle samples from MH-susceptible patients and non-MH animals in collaboration with other consortium partners