Master Thesis in Osteoimmunology and celluar biomechanics

Project Title:

Influence of the adaptive immune system on extracellular matrix formation in a bone healing context

We are currently looking for a motivated student of biology, immunology, biochemistry, biotechnology or other applicable disciplines eager to perform a master thesis in the interdisciplinary field of osteoimmunology and cellular biomechanics. The position is available from the 1st of October 2019 onwards for a minimum duration of 6 month.

 

You are here:

Background and scope of the work:

We recently reported that cells of the adaptive immune system influence extracellular matrix (ECM) formation during bone fracture healing. Specifically, T cells contribute to the organization of collagenous matrices. Immunocompromised mice lacking mature T cells (TCRβδ‒/‒) displayed severe dysregulation in collagen deposition and osteoblast distribution, leading to impaired healing1. In patients, a delayed fracture healing was associated with an ‘aging’ of the adaptive immunity, which is accompanied by an enrichment of terminally differentiated CD8(+) effector memory T cells2. Therefore, positive and negative regulators of bone healing are existing within the T cell population, making the specific T cell composition an important influencing factor.

In this project, we will investigate how different T cell subsets from a naïve or experienced phenotype influence ECM expression and deposition in an in vitro tissue formation model. Tissue formation processes will be simulated by using macroporous 3D biomaterials under immune-modulated conditions. Therefore, fibroblasts seeded in the biomaterial will be treated with conditioned media of activated T cell subsets during ECM formation. The composition of the newly formed matrix will be analyzed using immunohistological stainings, qPCR, western blot, ELISA and mass spectrometry. The mechanical properties will be determined by mechanical compression tests and contraction analyzes. The gained insights will help to elucidate the influence of the immune system on early matrix formation and understand recent in vivo observations.

Your Responsibilities  

Osteochondral defects are wounds that comprise cartilage and the underlying bone. Due to the lack of spontaneous regenerative potential in cartilage, such defects undergo impaired healing. Tissue with non-optimal mechanical properties (fibrocartilage) is formed, leading to pain and eventually triggering the degeneration of the neighbouring healthy cartilage. Scaffolds with proper mechanical properties may support tissue regeneration, guiding wound healing towards the production of healthy, functional tissue. However, the optimal scaffold properties still need to be defined.

In this context, the Julius Wolff Institute is looking for a highly motivated individual for an internship or Master thesis. You will develop finite element models of an osteochondral defect to determine the local mechanical strains within the wound. These strains would then be used to predict healing progression using computer models. You will simulate different scaffolds, varying properties such as elastic modulus and porosity. Investigations of the effects of different scaffolds properties on tissue formation will be part of your goals. You will work in a friendly and collaborative environment, having the opportunity to discuss your project in a multidisciplinary team.

Your Profile:

  • Solid cell culture experience
  • Basic experience in gene expression analysis (qPCR) and western blotting
  • Enthusiasm and strong motivation as well as team work capabilities

What we provide:

  • Training and support in an interdisciplinary research field
  • Instruction on 3D cell culture and various analysis methods
  • A friendly, collaborative and communicative environment

 Contact           Sophie Schreivogel (sophie.schreivogel@charite.de)

                        Julius Wolff Institute, Charité - Universitätsmedizin Berlin