Applications for the MRC DTP iCASE studentships September 2019 Entry will open 18th January, 2019.
Projects for September 2019 Entry
Co-supervisor 1A: Dr Sophia Karagiannis
Co-supervisor 1B: Dr Gerd Wagner
Partner Details: Ludger Ltd
Design strategies for cancer therapy have largely focused on one of nine human antibody classes, IgG1. We have designed an alternative approach by engineering anti-cancer antibodies bearing IgE Fc class regions. IgE antibodies are known to support immune defences against parasites and to be associated with allergies. These activities may be harnessed against cancer as a novel cancer immunotherapy strategy, exemplified by our first-in-class IgE antibody recognising a tumour-associated antigen undergoing a Phase I clinical trial at Guy’s Hospital.
IgEs are highly glycosylated antibodies, yet the precise effects of IgE glycan moieties on the potency and immune cell-activating mechanisms of IgE against cancer remain unclear. In this study, we aim to explore optimal engineering and glycoengineering strategies for the generation of anti-tumour IgE class antibodies in order to identify optimised antibodies for immuno-oncology. We will generate IgEs of the same specificity expressed in different mammalian expression systems and we will characterise their carbohydrate profiles in relation to function. Furthermore, we will generate different IgE glycoforms by administering inhibitors of glycan biosynthesis (Wagner). Antibody variant generation and pharmacological evaluations will be conducted in Year 1. Years 2-3 will focus on elucidating antibody biological functions, potency and ex vivo safety studies in patient blood and sera. Furthermore, glycoprofiling analyses (Ludger Ltd) will be conducted and correlated with antibody functional profiles. The study is designed to aid the identification of IgE antibodies and glycovariants with defined functional profiles and harbours considerable potential to deliver optimised antibody immunotherapies for clinical testing in oncology.
Co-supervisor 1A: Dr Sandrine Thuret
Co-supervisor 1B: Dr Marc-David Ruepp
Partner Details: https://www.msd-uk.com/index.xhtml
As the ageing population increases, this project addresses a timely/important question: How to maintain cognitive health during ageing? Finding how to counteract/reverse the process driving age-related neurological decay is one of the great endeavours of the 21st Century. Ultimately, slowing-down the rate of neurobiological ageing will reduce the incidence of all age-associated neurodegenerative diseases.
The overarching goal of this project is to address this challenge by identifying (I) molecular signatures of ageing neural stem cells (NSC) and (ii) anti-neuroageing human-NSC and geroneuroprotectors.
The PhD student will be trained and exploit multi-disciplinary methodologies developed in the Thuret and Ruepp labs such as stem cell culture, inducible gene expression systems, transcriptomics analyses and connectivity mapping. For drug repositioning. The student will also be working with/at our industrial partner MSD-UK for Objective-3 with access to advanced equipment and industrial expertise. The objectives are:
- Objective-1: Uncovering molecular signatures of NSC ageing (Year 1)
- Objective-2: Identifying geroneuroprotectors (Year 1)
- Objective-3: Validating the identified geroneuroprotectors
- Ojective-4: Generating a novel accelerated model of NSC ageing + Cross-validation (Year 3 / 4)
On completion, the student will be proficient with state-of-the-art methodologies and have delivered modulators controlling NSC ageing for future interventions to maintain NSC function and sustain cognition during ageing.
All iCASE projects are available as a straight 4 year PhD. Applicants may apply for one project only. You may contact project supervisors for further information about project opportunities. This does not commit a candidate to these laboratories. iCASE Projects available will be published on 18th January, 2019.
When choosing an iCASE project from those available for September 2019 Entry, in the funding section of the online application from please enter the funding code ‘MRCDTP2019_’ followed by the project number that corresponds to yourchosen project e.g:
Deadline for applications: Friday 1st March, 23:59