Use of vibrational microspectroscopies to elucidate a specific chemical signature associated with the low oxygen levels found in tumours

The purpose of this project is to study the chemical changes occurring in cells when cultured in low oxygen (hypoxia), using infrared and Raman microspectroscopies. Vibrational spectroscopies can measure the chemical composition of cells and tissue non-destructively. Coupled to a synchrotron source such as SOLEIL, an infrared microscope gives spatial resolution compatible with single cell analysis. SOLEIL is currently one of the topmost available synchrotron sources for infrared spectroscopy and the SMIS beamline is dedicated to infrared microspectroscopy with a strong focus on biological and biomedical applications. Many studies have identified biochemical changes in tumours by vibrational spectroscopy, which have been hypothetically related to hypoxia. Solid tumours are characterised by area of hypoxia due to the fast cell proliferation. Hypoxic tumours are correlated with tumour aggressiveness, resistance to therapy and poor prognosis. The effects of hypoxia on the intracellular chemical changes have not been investigated yet. The aim of this project is to compare cancer cells cultured in normoxic and hypoxic conditions to define a chemical signature associated with hypoxia. This study on cells cultured in vitro will be combined with the measurements in 3D spheroid culture system and in tumours formed in a chick embryo model, to monitor intracellular changes on tumour models. The student will also investigate if the hypoxic signature is present on brain tumour biopsies from patients (collaboration with the Walton Centre, Liverpool). We anticipate that this will provide a way to classify the tumour samples based on their chemical signature caused by the different oxygen levels. It will be correlated with patient outcome and is likely to have therapeutic implication. This is an interdisciplinary project involving experiments on large instrumentations in SOLEIL synchrotron (Paris) as well as live cell imaging and interaction with clinicians in Liverpool. Applications are welcomed from candidates with a background in Physical Sciences; training will be provided in cell biology.

Training:
The student will receive training in vibrational spectroscopy, infrared and Raman, as well as in complementary synchrotron-based techniques, and in data analysis methods such as multivariate pattern recognition. Collaboration with other synchrotron beamlines will be sought for exploring other types of spectroscopies. Training will also be provided for cell culture in normal and hypoxic environment, live cell confocal microscopy and also primary culture of glioblastoma cells (brain tumours) obtained from surgery. The candidate will benefit of the experience in two complementary and synergistic laboratories and research institutions. Indeed, The student will have the opportunity to spend time and receive training in 2 different laboratories located in Paris (SOLEIL) and at the Institute of Integrative Biology in Liverpool. The project offers considerable opportunity for an able and motivated student to independently develop his or her own research interests.