Thesis work: diabetes and obesity-related diseases, AstraZeneca

Job description
Elucidating the molecular mechanisms behind GPR75 activity and its role in protecting against diabetes and obesity-related disease

Thesis type: 60 credits
Project start: January 2023
Student location: On Site, Gothenburg Sweden

Do you want to impact early drug discovery by investigating molecular function of drug targets and help drive the development of life-changing medicines? Then AstraZeneca might be of interest to you!

We have a great opportunity for a master’s student to investigate the biological function and mechanism of a promising drug target: an orphan GPCR with previously unknown function.

Project information:
Approximately 35% of all approved drugs target G protein-coupled receptors (GPCRs) (1). GPR75 is an orphan G-protein coupled receptor (GPCR), where loss-of-function mutations were found  to be strongly correlated with protection from obesity and diabetes, and studies in genetic knock-out mice show that loss of GPR75 function protects against high-fat diet induces weight gain (2). In a collaboration with Regeneron, AstraZeneca aim to develop GPR75 antagonists as a therapeutic against diabetes and other obestiy-related and metabolic diseases (3).

The aim of this project is to use available tools to investigate the downstream signalling of GPR75, looking at G-protein signalling assays and receptor localization to further understand the mode-of-action of potential drugs targeting this receptor.

References:
Sriram and Insel.  Mol Pharmacol. 2018. G Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs? Apr;93(4):251-258. doi: 10.1124/mol.117.111062. Epub 2018 Jan 3. PMID: 29298813; PMCID: PMC5820538.
Akbari et al., Science. 2021. Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity. Jul 2;373(6550):eabf8683. doi: 10.1126/science.abf8683. PMID: 34210852.
 https://firstwordpharma.com/story/5359231


Responsibilities
In this project you will learn about the concept of GPCR biology and use a variety of methods and tools to investigate downstream G-protein signalling. On a daily basis you will work in the Cellular Assay Development team with colleagues/experts working on developing cellular assays using state-of-the-art technologies to support drug discovery projects.

You will gain experience and practical independency in techniques/skills such as experimental design and assay development, functional reporter assays, confocal imaging, cell culturing, cell transfection, compound screening and thesis writing. You will independently be conducting laboratory work, analyse data and present findings to your peers, and you will have the opportunity to actively and critically participate in the high-value research to understand underlying biology of a therapeutic drug target, potentially leading to publication in peer-reviewed journals.

You will have the opportunity to explore world-leading science, gain experience in a broad range of laboratory methods, obtain knowledge and experience in the pharmaceutical industry and extend your professional network.

Qualifications
Essential Requirements 
Close to graduation in successful master’s studies with excellent grades in the field of cell biology, molecular biology or biotechnology
Experience in laboratory techniques and experimental planning
Excellent communication skills in English (speaking, presenting and writing).

Desirable Requirements 
Knowledgeable in GPCR biology and downstream signaling
Experience working in a cell culture laboratory
Cell imaging and image analysis


About the company
At AstraZeneca, all of our employees make a difference to patients’ lives every day. We operate in more than 100 countries around the world and are one of Sweden’s most important export companies. With more than 2,400 employees from 50 countries, the vibrant Gothenburg site helps to support the entire life-cycle of AstraZeneca medicines, from drug discovery and clinical trials, to global commercialisation and product maintenance. Gothenburg is one of AstraZeneca’s three strategic, global R&D centres, alongside Cambridge and Gaithersburg, and plays a central role in our mission to deliver life-changing medicines to patients.