Infecties huid en weke delen door niet-tuberculose mycobacteriën
Infecties huid en weke delen door niet-tuberculose mycobacteriën
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Bestuurslid der MFVN · 168 · Infecties huid en weke delen door niet-tuberculose mycobacteriënVacature PhD candidate 'Clinical-translational study on skin and soft tissue infections caused by non-tuberculous mycobacteria'
36 per week
Scale: 10a/10
Job description
We look for a dedicated scientist (PhD candidate) for a clinical-translation study on skin and soft tissue infections caused by non-tuberculous mycobacteria (NTM).
Non-tuberculous mycobacteria (NTM) are environmental bacteria that are innocent to most people, but that may cause severe and difficult-to-treat disease in elderly people and immunocompromised people. These infections are hard to treat. Despite months of treatment with multiple antibiotics and often (repeated) surgery, skin lesions may persist or worsen. Regardless of this intensive treatment, skin lesions get worse in a subset of patients, sometimes because bacteria keep growing (antibiotic failure) or because of an excessive immune response.
In this project, we will perform longitudinal, in-depth research of the site-of-disease (skin) and systemic investigations on 30 patients from two Dutch third-tier NTM-SSTI reference centres to:- Unravel which clinical and immunological parameters predict the course of disease.
- Discover predictors and key mediators (i.e., potential therapeutic targets) in excessive inflammation during treatment that occurs in a subset of patients.
- Correlate site-of-disease antibiotic drug concentrations with microbiological response.
Tasks and responsibilities
- Inclusion of patients with skin and soft tissue infections due to nontuberculous mycobacteria for this specific project, and you will also be involved including patients with other mycobacterial infections into ongoing Mycobacterial Cohort Study.
- Coordination of high-quality blood and skin sampling.
- Processing of skin samples in preparation of scRNA sequencing together with dedicated colleagues.
- Conducting ex-vivo experiments on peripheral blood mononuclear cells.
- Take part in pharmacological measurements to determine skin concentrations of the key antibiotic drugs.
Relevant literature
On site-of-disease immunity to Mycobacterial infectionsImmune cell characteristics and cytokine responses in adult HIV-negative tuberculous meningitis: an observational cohort study. Scientific Reports 2019.
Cerebral tryptophan metabolism and outcome of tuberculous meningitis:
An observational cohort study. The Lancet Infectious Diseases 2018.
On site-of-disease Pharmacokinetics in Mycobacterial Infections
Model-based meta-analysis of rifampicin exposure and mortality in Indonesian tuberculosis meningitis trials. Clinical infectious diseases 2019.
On innate Immunity of Mycobacterial Infections
Low Induction of Proinflammatory Cytokines Parallels Evolutionary Success of Modern Strains within the Mycobacterium tuberculosis Beijing Genotype. Infection and Immunity 2013.
On immunotherapy for infections
Interleukin-1 receptor antagonist anakinra as treatment for paradoxical responses in HIV-negative tuberculosis patients: A case series. Med 2022.Profile
We are looking for a PhD candidate with a MSc in biomedical sciences or medicine with interest in disease mechanism and proven affinity for immunology and molecular sciences. You have good social skills. You will collaborate with fellow PhD and with MSc students to run the Mycobacterial Cohort Study, which means you will coordinate sampling with nurses and doctors of different departments and hospitals. Moreover, you have fluent communication skills in Dutch (C1 level) to engage with our patients and hospital staff and in English to engage with our scientific community.
Contact information
Any questions? Please contact Dr. Arjan van Laarhoven, Internist-infectious diseases specialist. Use the Apply button to submit your application.
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