Targeting calcitonin receptor to treat glioblastoma with glycan-based site-specific coupling of toxins to nanobodies

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Doctor consoling patient with brain tumour

Please note that applications are no longer being accepted for these positions

Finding a treatment for the brain tumor glioblastoma (GBM) is an unmet need in medicine and a global challenge. The Berlin Universities Alliance (BUA) in collaboration with the University of Melbourne (UoM) is offering unique and exciting opportunities for two potential PhD candidates, one with their home at Charité – Universitätsmedizin Berlin (BUA) and the other at UoM. The overall research program investigates the site-specific coupling via glycans in Berlin and demonstration of efficacy in animal models in Melbourne, using the complementary expertise of the research groups.

To these ends, the UoM home-based study will focus on cell biology, cell-based assays and orthotopic, intracranial animal models to define the potential of refined targeted toxins synthesized in Berlin by the partner PhD candidate. The Charité based PhD study will focus on glycosylation of proteins in vitro, toxin expression in bacteria and coupling of the toxin to glycosylated nanobodies.

Each candidate will spend a minimum of 12 months at the partner institution mid-term. Unique targeted toxins, based on an antibody and nanobody against calcitonin receptor (widely expressed in GBM) developed by Peter Wookey at UoM, will be synthesized and refined by the group headed by Hendrik Fuchs, with expertise in click chemistry, plant toxins and endosomal escape. The PhD candidates will be jointly supervised, but studies focussing on glycosylation of proteins in vitro, toxin expression in bacteria and coupling of the toxin to glycosylated nanobodies will be carried out in Berlin, while analysis of cell biology, testing in cell culture and xenograft animal models will be conducted in Melbourne. All candidates admitted to the Joint PhD program have access to a scholarship package that includes a living allowance and fee waiver, health insurance, and relocation support.

Project goals

These projects aim to develop a new strategy to treat glioblastoma by coupling highly specific antibodies and nanobodies to plant enzymes that confer high toxicity for targeted cancer cells. Novelty includes a new site-specific coupling technique that allows the generation of homogenous tailormade products in contrast to current antibody-drug conjugates that are heterogenous and undefined in structure. These fluorescence-tagged immunotoxins will be tested in cell culture and animal models including intracranial, orthotopic xenograft models to monitor penetration and targeted cell types, and efficacy to inhibit tumour expansion.

Supervision team

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Who we are looking for

We are seeking a PhD candidate with the following skills:

  • A Masters qualification in molecular biology or biochemistry with strong chemical background or in click-chemistry chemistry with strong biochemical background for the position hosted in Berlin, and a Masters qualification or equivalent in molecular and cell biology, preferably with an emphasis on cell imaging, mouse studies and cancer stem cells for the position hosted in Melbourne.
  • Demonstrated experience in the field of click-chemistry, glycan chemistry, amino acids, bacterial protein expression, and preferably molecular biology for the position hosted in Berlin, and experience in the field of cell biology, confocal imaging and mouse studies for the position hosted in Melbourne.
  • Demonstrated ability to work independently and as part of a team.
  • Demonstrated time and project management skills.
  • Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date).
  • Excellent written and oral communication skills.
  • Demonstrated organisational skills, time management and ability to work to priorities.
  • Demonstrated problem-solving abilities.

Further details

  • Two PhD projects are available. One candidate will be based at the University of Melbourne with a minimum twelve-month stay at Charité – Universitätsmedizin Berlin. The Berlin University Alliance-based candidate will be based in Berlin and will spend a minimum of 12 months at UoM.
  • The PhD candidates will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.
  • Dr Peter Wookey at the University of Melbourne will contribute expertise in nanobodies, cell biology, confocal imaging and animal studies including intracranial mouse models.  Prof Hendrik Fuchs at Charité – Universitätsmedizin Berlin will contribute expertise in the development and design of targeted toxins, controlled intracellular delivery of macromolecules, and endosomal escape.
  • The candidates will be enrolled in the Department of Medicine – Austin Health PhD program at the University of Melbourne, and in Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie at Charité – Universitätsmedizin Berlin.

Please note that applications are no longer being accepted for these positions

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