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Ongoing Project Advertisements

1. Yusuf Hamied Department of Chemistry: Synthetic Organic Chemistry
Prof. Robert Phipps (University of Cambridge) and Dr Thomas McGuire John Murphy (AstraZeneca)

Project Title:  The Development of Chiral Ligands and Catalysts for the Control of Enantioselectivity in Palladium-catalysed Cross-coupling Reactions. 

The project will be built on earlier work from the Phipps group, which was also carried out in collaboration with AstraZeneca (J. Am. Chem. Soc., 2022, 144, 15026). The aim of the project will be to develop the range of reactions that can be realised in a highly enantioselective manner using sulfonated chiral phosphines. This will involve both ligand synthesis and reaction evaluation. The student will spend some time working at an AstraZeneca site to make use of their facilities and expertise.

To apply, please click here

2. Department of Pharmacology
Prof. Laura Itzhaki (University of Cambridge) and Dr Mark McAlister (AstraZeneca)

Project Title: Novel Methods for the Rational Development of Molecular Glues

The student will be working on a collaborative project jointly supervised by Prof Laura Itzhaki in Pharmacology and Dr Mark McAlister at AstraZeneca and will work across the two sites. The project is in the field of targeted protein degradation, an emerging area of drug discovery that has generated much excitement in both academia and industry.

To apply, please click here

3. Department of Pathology
Dr Brian Ferguson (University of Cambridge)  and Dr Gunnel Hallden (AstraZeneca)

Project Title: Generation and Testing of New Vaccinia virus-based Oncolytic Virotherapeutic Agents

The student will be working under the supervision of Dr Brian Ferguson and Dr Gunnel Hallden developing and testing novel oncolytic viruses based on vaccinia virus. This joint project will exploit the Ferguson lab's expertise in anti-viral innate immunity and experience in generation of recombinant poxviruses with the resources and backing of the oncolytic virotherapy team at Astra Zeneca lead by Dr Hallden. The project will aim to generate a range of novel oncolytic recombinant vaccinia viruses and test them in vitro, in organoids and in animal models of cancer. A range of techniques will be used to generate viruses, assess their efficacy in murine tumour models, and analyse the innate and cellular immune responses during treatment.

To apply, please check  here

4. MRC Toxicology Unit
Dr Sarah Aitken (University of Cambridge) and  Dr Anne Ashford (AstraZeneca)

Project Title: Error-corrected sequencing of carcinogenic nitrosamines in a human liver spheroid model

Applications are invited for a 3.5 year PhD studentship based within the MRC Toxicology Unit, University of Cambridge, with extended industry experience at AstraZeneca (Cambridge, UK). The student will be working on a collaborative project jointly supervised by Dr Sarah Aitken (MRC Toxicology Unit, University of Cambridge) and Dr Anne Ashford (Genetic Toxicology, AstraZeneca).

MRC Toxicology Unit is seeking a highly motivated individual to undertake a combined experimental/computational project on drug-induced genotoxicity using human models. This is a mixed wet/dry lab project combining human liver models and sequencing. The purpose of the studentship is to apply NGS approaches to (i) understand mechanisms of nitrosamine-induced mutagenesis and (ii) advance the scientific understanding of carcinogenic risks associated with the exposure to nitrosamine impurities.

To apply, please check here

5. Yusuf Hamied Department of Chemistry: Synthetic Organic Chemistry
Prof. David Spring (University of Cambridge) and Dr Frank Narjes (AstraZeneca)

Project Title: Targeting undruggables: Degrading proteins recognising phosphate moieties

The project will involve the development of PROTAC methodology in degrading a diverse set of intracellular proteins that are yet not tractable, such as phosphatases. The aim of the project will be to develop the range of potent small molecule ligands with stable phosphate mimetics which are cell permeable. This will involve both organic synthesis and medicinal chemistry skills. The student will spend some time working at an AstraZeneca site to make use of their facilities and expertise.

To apply, please check here

6. Department of Biochemistry
 Professor Eric Miska (Biochemistry) and Dr Alessandro Bonetti (AstraZeneca) 

Project Title: The structure-function relationship for nuclear non-coding RNAs in healthy and disease lung epithelial cells

Long non-coding RNAs (lncRNAs) have emerged as key regulators of biological processes. Most lncRNAs are enriched in the nucleus and involved the regulation of gene expression. Not just the primary sequence but the structure and interaction partners of these lncRNAs are critical for their function. However, we do not currently have a thorough understanding of their direct targets and mechanism of action. Recent technological advances that allow the unbiased identification of RNA-RNA and RNA-DNA interactions have begun to unveil complex interaction networks of non-coding transcripts that regulate gene expression. The laboratory of Prof. Miska has developed COMRADES, a methodology that enables the transcriptome-wide identification of RNA structure and interactions. More recently, Dr. Bonetti has developed RADICL-seq, a technology that identifies genome-wide RNA-DNA interactions.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease causing progressive lung fibrosis. Currently, no cure is available for IPF patients. Non-coding RNAs have been implicated in human lung development and disease. Here we propose to investigate the structure/function relationship for nuclear non-coding transcripts by combining these two novel technological approaches in healthy and disease primary lung epithelial cells. The overarching goal is to identify structural motifs in lncRNAs as novel therapeutic targets in IPF.

To apply, please check here

7. Department of Chemical Engineering & Biotechnology
Prof. Mick Mantle (University of Cambridge) and Dr Richard Storey & Dr Les Hughes (AstraZeneca)

Project Title: Magnetic Resonance Imaging studies of freeze drying and reconstitution of pharmaceuticals

The project is in the field pharmaceutical/biopharmaceutical development that has generated much excitement in both academia and industry. Freeze drying has the ability to improve stability of both large and small molecules permitting more temperate storage conditions and hence energy saving across the lifetime of the product. The technique is widely used for small molecules, "next generation therapeutics" and larger biopharmaceuticals. This proposal aims to build upon our previous research(1), (2) with new avenues of research: (i) we will build an MRI compatible freeze drying/lyophilization rig that fits within a MRI magnet in Cambridge, allowing us to monitor, in real time, freeze drying; (ii) 3D characterization of the freeze dried solid cake porosity and tortuosity using gas and liquid phase MRI; (iii) Establish the link between freeze-drier operating conditions and product reconstitution performance.

The magnetic resonance research centre at the Department of Chemical Engineering & Biotechnology in Cambridge is a world class facility housing a vibrant and diverse research group. The are 8 superconducting NMR/MRI instruments along with a number of lower field permanent magnet systems which cover a large range of magnetic fields.

To apply, please check here

8.  Department of Pathology
Dr Brian Ferguson (University of Cambridge) and Dr Gunnel Hallden (AstraZeneca)

Project Title: Generation and testing of new Vaccinia virus-based oncolytic virotherapuetic agents

The project will aim to generate a range of novel oncolytic recombinant vaccinia viruses and test them in vitro, in organoids and in animal models of cancer. A range of techniques will be used to generate viruses, assess their efficacy in murine tumour models, and analyse the innate and cellular immune responses during treatment.

To apply, please check here

9. Wellcome Trust- Medical Research Council Cambridge Stem Cell Institute 
Dr Harry Bulstrode (University of Cambridge) and Prof Petra Hamerlik (AstraZeneca)

Project Title: Functional interplay between PARP1 inhibition and microenvironment in glioblastoma

Glioblastoma (GBM) remains uniformly and rapidly fatal, and a leading cause of life years lost to cancer. Tumour cells recruit a microenvironment rich in Tumour Associated Macrophages (TAMs). TAMs adopt characteristic tumour-permissive states, offer trophic support to tumour cells, and suppress recruitment and activation of immune effector cells, contributing to the failure of immunotherapy. In this context, the clinical response to immune checkpoint blockade and adoptive T-cell therapy in GBM fall far short of that achieved in other solid organ tumours.

The project will be based on established primary human patient tissue slice culture, cell line and mouse model systems. You will be applying an array of routine molecular biology analysis techniques, as well as novel state-of-the-art approaches- human tissue RNA sm-FISH, imaging mass cytometry and spatial transcriptomics.

To apply, please check here

10. Wellcome Trust- Medical Research Council Cambridge Stem Cell Institute 
Dr Matthias Zilbauer, Dr Namshik Han (Unviersity of Cambridge) and Dr Daniel Corridoni, Dr Tatiana Ort (AstraZeneca)

Project Title: Developing novel molecular classifier and novel treatment approaches for childhood onset Inflammatory Bowel Diseases

Inflammatory Bowel Diseases (IBD) such as Crohn's Disease (CD) and Ulcerative Colitis (UC) cause chronic, relapsing inflammation of the intestine. In the absence of a cure, patients suffer a lifetime of debilitating symptoms. In spite of the major healthcare burden caused by these conditions and in light of rapidly increasing incidences globally, we urgently need to advance our understanding of disease pathogenesis in order to develop improved treatments. This project aims to develop and apply novel computational methods to existing and newly generated molecular multimodal datasets derived from primary human tissue samples as well as patient-derived intestinal organoids. Specifically, we will develop novel molecular disease classifiers in order to personalise treatment of IBD patients. Furthermore, analyses of cell type specific as well as single cell molecular profiles will allow us to develop novel treatment targets which will then be tested on our patient-derived organoid models to identify the most promising candidates for further development into novel treatments.

 This PhD program offers the unique opportunity to work at the interface of basic science and clinical medicine aiming to train independent, innovative scientists capable of delivering translational research using cutting edge computational methodologies.

To apply, please check here

11. Department of Medicine
Dr. Menna Clatworthy (University of Cambridge) and Dr Georgina Bowyer (AstraZeneca)

Project Title: Ex vivo modelling of human lymphoid organs to interrogate the mechanisms of action of myeloid checkpoint inhibitors

Checkpoint inhibitors targeting inhibitory molecules on T cells (PD1, CTLA4) to reinvigorate tumour killing, have had great clinical success in some cancers but not others, and even in those cancers with good responses, 60-80% of patients fail to respond. Myeloid cells are a major component of the tumour microenvironment, and can be either pro- or anti-tumourogenic. Therefore, one major strategy being developed is myeloid checkpoint inhibition which, combined with traditional checkpoint inhibitors, may release T-cell killing and expand the proportion of responsive patients.

The mechanisms of these checkpoint inhibitors can be difficult to model in vivo or using cell lines. Using human tissue, this project will utilise the Clatworthy lab's world-leading capabilities in advanced imaging and single-cell RNA sequencing, together with AstraZeneca's experience in co-culture assays to develop complex 3D models that better recapitulate the tumour microenvironment and use these to gain a deeper mechanistic understanding of candidate drugs.

The successful candidate should have (or expect to obtain by the start date) at least a 2:1 honours degree (or equivalent) in a relevant subject. This PhD offers the unique opportunity to work at the interface of basic science and clinical medicine in both academic and industry settings. The successful candidate will have a deep interest in cancer immunology and wish to apply this to clinically relevant problems. They should be enthusiastic, focused and able to work well both independently and as part of a team. Prior experience in cell culture or working with primary human tissue would be advantageous but full training will be given.

To apply, please check here