An integrated human organ on chip model for the prediction of BBB penetration and CNS exposure.

The development of effective Alzheimer’s disease (AD) therapies continues to be challenging, with 98% of therapies failing in Phase III due to a lack of efficacy (often driven by poor brain exposure). In vitro methodologies to assess CNS disposition are routinely utilised in drug discovery. However, these technologies still fall short of adequately mimicking the human blood-brain barrier (BBB).

To reduce/refine/replace (3R) the use of animal models, the Food and Drug Administration (FDA) has strongly encouraged the use of cell-based assays and computer models in preclinical trials. To that end, specific emphasis has been put on the development of organ-on-chip / microphysiological systems (MPS).

Hypothesis: Innovative chip-based human BBB models will enable improved prediction of CNS drug exposure in healthy volunteers and patients and be applicable to current and novel modalities.

Using cutting edge cell biology tools, this studentship will generate a 3-organ MPS consisting of human brain organoids and liver microtissues separated by a BBB made of brain endothelial-like cells. The successful student will explore and characterize this model to determine if it generates a more physiologically relevant phenotype and increases the accuracy and prediction of exposure for small molecules and new modalities including gene therapy. This is an exciting project at the forefront of science that will provide the student with training and expertise in stem cell biology, BBB, organ-on a chip technologies, and experience in working with an international pharmaceutical partner recognized in the CNS space.

The project is suited to a candidate with a degree related to biological or life sciences with a strong interest in neuropharmacology, and/or neurodegeneration. Experience with cell culture, especially stem cells and primary cells as well as 3D organoids would be advantageous. The student will be based in University of Liverpool with visits to Belgium within the laboratory of our industrial collaborator enabling an experience of working with an international  global biopharma company as well as academia.

Please contact Dr David Dickens (David.dickens@liverpool.ac.uk) via email with a subject tile of “BBB PhD Studentship” for additional information and to enquire on the application process.

Applications will be reviewed until a suitable candidate is appointed. The PhD project will start in October 2024 and be based in University of Liverpool with visits to Belgium

Supervisors:

Dr David Dickens - [David.dickens@liverpool.ac.uk]

Dr. Beth Williamson -  DMPK, UCB Biopharma

Dr. Benoit Cox -  In vitro ADME, UCB Biopharma