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Leukocyte Signalling

Our laboratory is studying the molecular mechanisms of how various leukocyte proteins regulate signal transduction by surface receptors and how their dysfunction triggers disease. Within this relatively broad field, our research focuses mainly on membrane adaptor proteins and Src-family kinases (SFK) and on their roles in inflammation and haematopoiesis… More about the laboratory

Project: Signaling pathways in inflammation and autoinflammatory disease

Supervisor

TBA

Project description

The project will focus on explaining the mechanisms contributing to the development of autoinflammatory disease chronic recurrent multifocal osteomyelitis (CRMO). It is a chronic disorder characterized by the spontaneous development of inflammatory lesions in the bones. The molecular basis of the disease is unknown. The candidate will explore alterations of pro-inflammatory signaling pathways in white blood cells from patients with CRMO and from a mouse model of the disease and analyze the mechanisms of CRMO pathogenesis. The project will also involve developing and testing potential treatment strategies in the mouse model. In addition, the candidate will contribute to projects investigating the function of other adaptor proteins involved in the regulation of leukocyte signaling and inflammation.

Candidate profile

The candidate must hold a Master degree (or be close to its completion) in immunology, molecular/cell biology, biochemistry or in related field of life sciences. The applicant must have a strong interest in immunology and related biomedical sciences. Ability to communicate in English is required.

Suggested reading

  • Zhao Y, Ferguson PJ. Chronic non-bacterial osteomyelitis and autoinflammatory bone diseases. Clin Immunol 2020; 216: 108458. [pubmed] [doi]
  • Pavliuchenko N, Duric I, Kralova J, Fabisik M, Spoutil F, Prochazka J, Kasparek P, Pokorna J, Skopcova T, Sedlacek R, Brdicka T. Molecular interactions of adaptor protein PSTPIP2 control neutrophil-mediated responses leading to autoinflammation. Frontiers in Immunology 2022; 13. [doi]
  • Kralova J, Pavliuchenko N, Fabisik M, Ilievova K, Spoutil F, Prochazka J, Pokorna J, Sedlacek R, Brdicka T. The receptor-type protein tyrosine phosphatase CD45 promotes onset and severity of IL-1β-mediated autoinflammatory osteomyelitis. J Biol Chem. 2021 297(4): 101131. [pubmed] [doi]
  • Kralova J, Drobek A, Prochazka J, Spoutil F, Fabisik M, Glatzova D, Borna S, Pokorna J, Skopcova T, Angelisova P, Gregor M, Kovarik P, Sedlacek R, Brdicka T. Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis. J Immunol 2020 204(6): 1607-1620. [pubmed] [doi]

Application: https://www.img.cas.cz/career/phd-programme/application/