Postdoctoral Fellow – Respiratory & Immunology, Early Discovery Research

Postdoctoral Fellow – Respiratory & Immunology, Early Discovery Research

Unraveling Efferocytosis: From Inflammation Resolution to Therapeutic Potential

Location: Gaithersburg, US

Department: Biopharmaceuticals

Our Postdoc Programme is for self-motivated individuals looking to take on interesting, high impact projects in a collaborative, challenging and reputable environment. Do you have expertise in, and passion for, respiratory disease understanding? Would you like to apply your knowledge to impact drug discovery projects in a company that follows the science and turns ideas into life-changing medicines? Then join the Respiratory & Immunology Group at AstraZeneca and unlock the power of what science can do.

Therapeutic Area Description:

In the Respiratory & Immunology (R&I) therapy area we are rewriting the future of patients suffering from immune-driven diseases, leading the way away from mere symptom control towards disease modification, remission and, one day, cure! By following the science, we are focused on sustainably addressing tough and complex unsolved problems.  Our strategy focuses on addressing the fundamental biology, creating effective new drug modalities and combinations, and implementing a precision medicine approach from the outset of drug discovery. 

Job Summary:

The postdoctoral researcher will employ established methodologies to generate a comprehensive macrophage secretome by co-culturing apoptotic cells and macrophages. Collaborating with omics groups, the researcher will profile the secretome (proteome and lipidome) and transcriptome of macrophages post-efferocytosis. They will work with the bioinformatics team to analyze data and identify novel activators and signaling changes in the macrophage secretome. Using established immune cell assays, the postdoc will verify the effects of the secretome and identified activators on immune mechanisms, signaling pathways, and cell functions. Additionally, they will explore the potential of engineering pre-resolved macrophages and test cell therapy opportunities in an in-vivo pilot study. These findings aim to advance therapeutic strategies for autoimmune treatments.

Embedded within a bioscience immunology team focused on drug discovery for autoimmune diseases, the postdoc will benefit from a supportive environment and collaboration with AstraZeneca and academic supervisors, providing a unique network of scientific and technical expertise relevant to the project.

Key Duties & Responsibilities:

This project presents an exciting opportunity for a postdoctoral fellow to delve into the mechanisms of inflammation resolution through efferocytosis.

Project Overview 

• Focus: Investigating mechanisms involved in resolving inflammation via efferocytosis.

• Importance: Understanding inflammation resolution is crucial to prevent tissue damage and autoimmune diseases from prolonged inflammation.

Background

Inflammation is a crucial immune response to disruptions in homeostasis, aiding in healing and restoring balance. However, prolonged inflammation can lead to tissue damage and autoimmune diseases. 

During inflammation, neutrophils and monocytes penetrate affected tissues to clear apoptotic cells and pathogens. Efferocytosis is the process of cell clearance by tissue-resident phagocytes or monocyte-derived macrophages. It plays a critical role in resolving tissue inflammation by preventing the release of damage-associated molecular patterns (DAMPs) that activate immune responses. During efferocytosis, macrophages acquire a novel pro-resolutive phenotype to support the resolution process. Both macrophages and apoptotic cells secrete pro-resolutive factors, including microRNAs, proteins, and lipids. These factors, collectively known as the "secretome," play a crucial role in resolution, restoration of homeostasis, and tissue repair.

The secretome from macrophages exhibits a uniquely robust pro-resolutive capacity and exceptional immune-suppressive properties compared to other secretomes. The significant immune-suppressive therapeutic efficacy of macrophage secretome was evaluated and evident in models of collagen-induced rheumatoid arthritis (RA) in mice, DSS-induced colitis, and cancer.Aberrations in efferocytosis, the generation of the pro-resolutive secretome, and the reprogramming of macrophages to pro-resolutive phenotypes have been observed in autoimmune diseases such as lupus and RA.

The suppressive activity of the macrophage secretome presents a potential novel therapeutic opportunity for the treatment of human autoimmunity. So far, key factors influencing the suppressive functions of the macrophage secretome have not been thoroughly examined. 

Research Goals 

Characterization: Identify the full spectrum of factors (proteins, lipids) associated with efferocytosis and macrophage reprogramming.

Mechanistic Insights: Explore how secretome components drive inflammation resolution through signaling changes and immune cell interactions.

Therapeutic Exploration: Assess potential therapeutic approaches targeting the suppressive activity of the macrophage secretome.

Essential Qualifications / Education:

• PhD in Immunology, Biochemistry, Molecular Biologyor related field 

• A maximum of 4 years of postdoctoral experience.

• Effective implementation of standard immunology and molecular biology lab assays and in vitro cell culture to answer research questions.

• Extensive knowledge of innate immunity mechanisms and other immunology mechanisms

• Publication record of novel and impactful research

Desirable Requirements:

• Background in inflammation research (lipid mediators, resolution processes) with a basic understanding of autoimmune disease biology, including cell types, signaling pathways, lipid mediators, and mechanisms.

• Experience with more complex culture models such as cell co-cultures, organoids, and sample preparation for lipidomics, proteomics, and RNA sequencing.

• Previous experience with RNA sequencing, proteomics, and lipidomics techniques.

• Previous experience with data science/bioinformatics and the analysis of large and complex data sets.

This research position offers a postdoc the opportunity to lead an independent project focused on how resolving inflammation can enhance therapeutic strategies for autoimmune diseases at the molecular and cellular levels. The postdoc will work closely with a team of enthusiastic scientists with expertise in cell and molecular biology, immunology, lipidomics, proteomics, transcriptomics, and bioinformatics.

With access to world-class research facilities and cutting-edge technologies in AstraZeneca, the postdoc will collaborate with external Academic supervisor, Distinguished Professor James Pestka from Michigan State University, providing a chance to expand their academic network. The project is anticipated to yield 3-4 publications in high-impact journals, boosting the postdoc's academic profile. Additionally, the position offers valuable industry experience and insights into drug discovery and development.

The postdoc will be directly mentored by a Senior Scientist at AstraZeneca and will collaborate with scientists and cross-functional teams within the department for comprehensive support. They will also work with experienced bioinformaticians to analyze omics data and collaborate closely with the in-vivo team to leverage the necessary in vivo capabilities for this project.

As part of the Early R&I research community, the postdoc will attend lab meetings and scientific seminars and join the global AZ postdoc community. Dr. James Pestka, the academic mentor from Michigan State University, will facilitate collaboration, offering insights into macrophage biology and autoimmunity

AZ’s Postdoc Programme: https://careers.astrazeneca.com/postdocs-astrazeneca

Life at AstraZeneca: https://careers.astrazeneca.com/life-at-astrazeneca

This is what we’re made of: https://www.youtube.com/watch?v=pmFx_jr2eFo&t=2s

Gaithersburg site:https://www.youtube.com/watch?v=GOvxXGjBd1w

Req Open Date: Apr 21, 2025

Req Close Date: May 25, 2025

Stages of interview: Applicants are reviewed for fit/skills and invited to each step. You may not be invited to each step. (1) One-way video interview and (2)

Virtual Interview Panel with presentation.

To find out more go to: astrazeneca.com and https://careers.astrazeneca.com/bpd