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The effect of circadian rhythm on the nano-bio interface

Principal Supervisor: Prof Sébastien Perrier - Department of Chemistry

Co-supervisor: Dr Robert Dallman - Warwick Medical School

PhD project title: The effect of circadian rhythm on the nano-bio interface

University of Registration: University of Warwick

Project outline:

The circadian (circa, about; dies, day) clocks can predictably control a range of cell mechanisms in mammalian cells. Circadian clocks consist of interwoven regulatory transcription/translation loops involving around 15 clock genes. The molecular clocks reside in the majority of mammalian cells, and are coordinated and reset through physiological rhythms, generated by the suprachiasmatic nuclei, a hypothalamic pacemaker. This Circadian Timing System (CTS) regulates a number of cell mechanisms, as well as cellular proliferation in mammals. Interestingly, although a vast amount of studies have investigated the mechanisms of targeting and penetration of nanomaterials into cells, very little is known on the influence of the clocks on cell uptake. Cell uptake of nanoparticles is a key element in the design of nanotherapeutics, which encapsulate and deliver drugs in targeted locations, thus increasing the therapeutic index of a given drug, and they vary extensively based on nanoparticles structure (Figure 1).

Here we seek a new approach to the measurement of circadian biomarkers, to assess the circadian rhythm of nanomaterial uptake and its mechanism. This original and unprecedented investigation will employ nanomaterials to both clarify clock-based cell mechanisms and also investigate the effect of circadian rhythm on nanoparticle uptake. The research will be carried out within a multidisciplinary team with expertise in materials science and in experimental medicine and chronotherapeutics.

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BBSRC Strategic Research Priority: Molecules, cells and systems

Techniques that will be undertaken during the project:

The project will combine materials, chemical and biological techniques:

  • Polymer and nanoparticle synthesis
  • Solid-phase peptide synthesis
  • Labelling of nanoparticles
  • Bioconjugation techniques
  • Polymer / nanoparticles characterization techniques: GPC, SLS and DLS, SAXS, SANS, TEM, SEM, DCS.
  • Small molecules characterization techniques: NMR, IR, UV, Fluorescence.
  • Maintenance of several human cancer cell lines
  • Study of the cell viability by MTT assay
  • Study of the cell internalization mechanism by Flow Cytometry and Confocal Microscopy
  • Immunostain main organelles and receptors.

Contact: Prof Sébastien Perrier, University of Warwick