train the next generation of scientists in order to tackle the challenges of diabetic bone
disease from various angles and with the newest technologies available. Interdisciplinary
training and implementation of innovative approaches are key. Within this consortium, we will
comprehensively unravel the genetic and environmental mechanisms that contribute to bone
fragility in diabetes, identify predictors and clinical markers for patient stratification, decipher
the underlying molecular mechanisms of bone fragility in diabetes, and establish potential
interventions through a personalised medicine approach.
The research programme will address different aspects of diabetic bone disease from the
viewpoints of epidemiology, genetics, miRNAs, microbiome, bone biology, bone
biomechanics and microstructure, preclinical and clinical research. It will utilise advanced
imaging and computational approaches, diabetes mouse models and access to clinical
cohorts and registry data to obtain a comprehensive overview of how these mechanisms
combine in diabetes to cause increased fracture risk.
With this interdisciplinary approach, we can explore the impact of biological pathways in
mouse models and/or humans, and interactions with diet, exercise and other exposures.
Collaborations with industry will allow early identification of IP, access to state of the art
technologies, and will complement the academic ESR training programme with
entrepreneurship and industrial mentoring.
Your PhD project:
You will investigate in vitro whether hyperglycemia in osteocyte cell lines (MLOY4, IDG-SW3
and Ocy454) affect mitochondrial activity, autophagy, apoptosis and signaling pathway
involved in mechanotransduction (PPARƳ, Postn, Sost…). In vivo you will characterizes
whether Pparγ inhibition in osteocyte, periostin recombinant, and sclerostin-antibody affect
autophagy and bone mechanical response in a model of high fat diet & Db/Db mice. The
mouse model will be characterized in terms of bone and glucose homeostasis. Two-exercise
model will be used treadmill and axial compression of long bone. The student will receive a
profound training in cell and molecular biology (culture of cell lines and primary cells,
transfections for siRNA/plasmids, WB, real-time PCR, immunofluorescence,
viability/apoptosis assays, ELISAs, etc.), animal experimentation, comprehensive bone
phenotyping (µCT, mineralization, serum analysis of bone turnover markers, biomechanical
testing of bones, histomorphometry) and glucose homeostasis (Euglycemic hyperinsulinmic
clamp, GTT, ITT, PET/CT, histology).
Finally, in collaboration with the clinical service periostin and sclerostin new markers of bone
quality and fragility will be test in relation to glucose homeostasis in the Geneva Retirees
You will embark on secondments to other FIDELIO partners (SDU (DK), UKE (DE)) to access
experimental models or tools or receive training not available in the home laboratory. This will
include comparing the similarity and difference between our in vitro model and the
bioenergetics of human osteoblasts from T2DM, collagen orientation, spatial measurement of
non-enzymatic cross-link ratio, and calculation of bone formation/resorption through microCT
imaging. Total secondment time is 3 to 6 months.
Further qualifications will be obtained through the collaboration with X. Edward Guo and N
Vilayphiou (Scanco) regarding bone response to loading and imagery technics.