Research Fellow

Job Purpose

A post doctoral scientist is required to join our multidisciplinary team of basic scientists and clinicians working on development and evaluation of a novel device and procedure for assessment of human liver functional integrity and reconditioning.

PROJECT SUMMARY.

The overarching goal of the study will be to explore the feasibility of linking up the Extracorporeal Liver Assist Device (ELAD) manufactured by Vital Therapies Inc., with the OrganAssist Normothermic Machine Liver Perfusion Device (NMLP) which we are currently evaluating for the preservation and reconditioning of donor livers deemed unusable for clinical transplantation. The purpose for undertaking this is to determine whether such an approach could enhance the potential of NMLP to rejuvenate such organs by harnessing the potential regenerative and detoxification capacity of the metabolically active hepatocyte cell line used in the ELAD. If successful the hybrid device would be a completely novel approach to marginal donor liver reconditioning.

AIMS and PLAN.

• Initially we will undertake extensive in vitro evaluation of the effects of ELAD conditioned medium (ELCM) on primary human hepatocytes which are routinely isolated, cultured and functionally assessed within the UoB Centre for Liver Research (Bhogal et al PLoS One 2011). This will include monitoring a range of readouts which reflect cell viability and function.
• Briefly, isolated hepatocytes will be cultured with increasing concentrations of ELCM or media alone for up to 24 hours. ELCM provided by VT or supernatants from hepatocytes cultured with ELCM, will be subjected to proteomic and metabolic analysis using the core facilities available at the UoB Centre for Genomic Proteomic and Metabolomic Analysis. Where target proteins or metabolites of interest are identified, this will be followed up with further more focused analysis as appropriate. This data should enable us to identify any potentially beneficial biologically active factor(s) contained within the ELCM. Confirmation will be sought using the approach of specific solid phase immunoprecipitation of ELCM providing antibodies are available. Hepatocyte production of albumin, urea, lactate and glucose (consumption) will be measured as conventional readouts of de novo protein synthesis and hepatocyte metabolism. Importantly these experiments will provide guidance as to the appropriate concentration of ELCM to use in the subsequent NMLP pilot study (aim 2).
• A selected series of disgarded donor or explanted livers consented for research use will be perfused with our standard NMLP perfusion fluid containing ELCM. We have a standard protocol for assessing paraeters of graft function, and for sampling of perfusate and tissue throughout the NMLP procedure, for biochemical and histological analysis (Mergental et al Am J Transplant 2016 In press). We will compare these with retrospective data obtained from over 40 standard NMLPs that we have already carried out.
• A hybrid device will be developed by the Vital Therapies ELAD team in consultation with the UoB NMLP team. We will then carry out a further pilot perfusion study comparing cohorts of similar quality liver on the hybrid device with an ELAD containing hepatocytes in circuit or an ELAD containing no hepatocytes.

Person Specification

• • A minimum upper second class degree in biomedical sciences together with a PhD in either immunology or any relevant area of BMS with relevant transferable skills.
• • High level analytical capability
• • Ability to communicate complex information clearly
• • Fluency in relevant models, techniques or methods and ability to contribute to developing new ones
• • Ability to assess resource requirements and use resources effectively
• • Understanding of and ability to contribute to broader management/administration processes