Development of a Novel Automatised Platform for Drug Discovery in Relevant Human Tissue Models at UCL

Project Title:

Development of a novel automatised platform for drug discovery in relevant human tissue models

Primary Supervisors: Prof. Danail Stoyanov | Prof. Paolo De Coppi

Secondary Supervisors: Dr Giovanni Giuseppe Giobbe | Dr Giuseppe Mazza

• UCL Great Ormond Street Institute of Child Health (UCL GOS ICH)
• Wellcome/ EPSRC Centre for Interventional and Surgical Sciences (WEISS)
• Engitix Therapeutics
• Zayed Centre for Research into Rare Disease in Children (ZCR)

A 4-year funded PhD studentship is available in the UCL GOS Institute of Child Health “Developmental Biology and Cancer” department. Studentship provides a stipend for four years (at UKRI level) and tuition fees (home status). Stipend details can be found here.

The successful candidate will join the UCL CDT in Intelligent, Integrated Imaging in Healthcare (i4health) cohort and benefit from the activities and events organised by the centre.

Project Background:

Drug discovery is known to be a long and expensive process with very low success outcomes.

The whole process usually develops over three phases:

1. synthesis of the drug molecules,
2. preclinical animal trials, and
3.  human clinical trials.

Preclinical animal trials have shown crucial limitations in the past years, as caused by the wide interspecies gaps between animals and humans. This often translates into wide unreliability in animal trials’ outcomes, with huge losses in pharmaceutical research and development programs.

The use of human-derived in vitro/ex vivo models has opened new horizons in this field, by preserving patients-specific features and reproducing physiological and pathological scenarios more reliably ^1,2.

The urgency in establishing novel therapeutic strategies is evident in the field of liver disease, as shown by the constant rise in cases³ and the complex multifactorial nature of hepatic pathologies.

Precision-cut tissue slices (PCTSs) and organoids have the potential to overcome these challenges. PCTSs are biological tissue sections that retain organs’ features, in either their physiological or pathological state, whilst organoids are 3D cellular aggregates with wide scientific and clinical applicability. These models have generated great interest from scientific and healthcare institutions, showing the potential to reduce (and replace) preclinical animal trials.

1. Weinhart, M., Hocke, A., Hippenstiel, S., Kurreck, J. & Hedtrich, S. 3D organ models—Revolution in pharmacological research? Pharmacological Research vol. 139 446–451 Preprint at https://doi.org/10.1016/j.phrs.2018.11.002 (2019).
2. FDA Modernization act 2021. https://www.congress.gov/bill/117th-congress/senate-bill/2952?r=77&s=1 (2021).
3. Asrani, S. K., Devarbhavi, H., Eaton, J. & Kamath, P. S. Burden of liver diseases in the world. Journal of Hepatology vol. 70 151–171 Preprint at https://doi.org/10.1016/j.jhep.2018.09.014 (2019).

Research aims:

This doctoral project concerns the development of an automatised platform devoted to the derivation of PCTSs and organoids from patient-derived surgical samples. This will concern the combination of mechanical components, electronic circuitry, and automatised modules. The platform will then be used to assess the efficacy of novel drug candidates by integrating biological and machine learning approaches.

The project aims at establishing a multidisciplinary approach to tackle current shortcomings in drug discovery processes by adopting a multifaceted perspective. If successful, this work will establish novel drug discovery pipelines that can be further expanded to a wide array of pathological scenarios.

Person specification:

Experience with:

• Design, manufacturing, and assembly of mechanical and electrical components
• Bioengineering, cellular and molecular biology
• Computer science and bioinformatics
• Laboratory practice

This studentship is for Home Fee applicants only.

Overseas fee payers will not be considered.

Find out more information about Fee Status criteria here

Further details including how to apply can be found by clicking the ‘Apply’ button, above.