Work Activities Immune cells are controlled by a balance of activating and inhibitory signals given by other cells and the environment. This balance is crucial for maintaining homeostasis as over- or under-activation can result in autoimmune or chronic diseases and cancer. Immune cells respond to their environment through immune receptors on the cell plasma membrane. Immune receptors activate by binding to ligands on other cells or within the extracellular matrix. Interestingly, these receptors do not contain intrinsic functionality but instead rely on the association with adaptor and signalling proteins to transmit activation or inhibitory signals into the cell and exert cellular responses [1]. This reliance on a network of molecules to activate or ‘trigger’ immune receptors is highly complex and, due to the enormous therapeutic potential of immune cells, a topic of great interest [2]. Most studies to date have focused on activating receptors such as the T cell receptor, however, inhibitory receptors have become a recent interest due to the success of immune checkpoint inhibitors in treating cancer, and the potential to treat autoimmune diseases through inhibitory receptor-driven immunosuppression. Importantly, it has become clear in recent years that inhibitory receptors are tightly regulated, and little is known about how they respond to ligands, particularly extracellular matrix ligands such as collagen. Studies on cell-cell interfaces helped to formulate a model of immune activation called the ‘kinetic segregation model’ which describes how it is necessary for some proteins to be excluded from the site of receptor activation at the immune synapse [3].
We want to determine if this model also applies to inhibitory immune receptors, and outside of the cell-cell interface context with the goal of increasing the understanding of inhibitory receptor activation. As an intern in the Physics of Cellular Interactions (PCI) group, headed by Dr. Kristina Ganzinger, you will investigate how inhibitory immune receptors interact with, and become activated by their environment. You will investigate the possible exclusion of phosphatases from the site of inhibitory receptor activation using advanced microscopy techniques. You will learn how to prepare artificial membrane surfaces, culture cells and label targets of interest on the cell membrane. In addition, you will learn to visualise these proteins on the cell membrane using high resolution confocal and total internal reflection fluorescence (TIRF) microscopy. Building on current experience in the PCI group, you will replicate an immune cell synapse to explore relative organisations of membrane proteins. Ultimately, this will allow you to build upon the understanding of the cell membrane architecture upon immune cell inhibition and to aid the development of treatments targeting inhibitory receptors in autoimmune diseases and cancer.
[1] Dushek O,
et al., Immune Rev. 2012
[2] Barton MI,
et al., Commun Biol. 2024
[3] Davis, S,
et al., Nature Immunology. 2006
Qualifications You already have a Bachelor’s degree in (bio)physics, molecular biology or biomedical sciences and now participate in a Master study in one of these areas who is interested in applying advanced microscopy techniques to an immunological question. You have a nationality of an EU-member state and/or you are a student at a Netherlands University. The internship has to be a mandatory part of your curriculum. We expect you to be available for at least 6 months, although longer is preferable.
Work environmentAMOLF is a part of NWO-I and initiate and performs leading fundamental research on the physics of complex forms of matter, and to create new functional materials, in partnership with academia and industry. The institute is located at Amsterdam Science Park and currently employs about 140 researchers and 80 support employees.
www.amolf.nlPhysics of Cellular Interactions (Ganzinger) group – We are a supportive and social research group of about 8 PhD students and postdocs, which work together in small teams on various projects from immunological signalling to signalling in synthetic cells. The collaborative and social atmosphere includes to the other research groups at the AMOLF institute at the Science Park in Amsterdam. Our group has been making recent technical advances, including a new single-molecule tracking method based on DNA-PAINT that we recently developed (Nat Commun 2021, Nat Commun 2023), new in vitro assays (ACS Syn Biol 2021, ACS Omega 2024), and imaging approaches developed by our lab and others (JACS 2013, Nat Immun 2016, PNAS 2019), all to closely investigate the intricate molecular details of cellular signaling.
https://amolf.nl/research-groups/physics-of-cellular-interactionsWorking conditions At the start of the traineeship your trainee plan will be set out, in consultation with your AMOLF supervisor.
More information? For further information about the position, please contact Kristina Ganzinger: k.ganzinger@amolf.nl or Megan Farell m.farrell@amolf.nl.
Application You can respond to this vacancy online via the button below.
Online screening may be part of the selection.Diversity code AMOLF is highly committed to an inclusive and diverse work environment: we want to develop talent and creativity by bringing together people from different backgrounds and cultures. We recruit and select on the basis of competencies and talents. We strongly encourage anyone with the right qualifications to apply for the vacancy, regardless of age, gender, origin, sexual orientation or physical ability.
AMOLF has won the NNV Diversity Award 2022, which is awarded every two years by the Netherlands Physical Society for demonstrating the most successful implementation of equality, diversity and inclusion (EDI).
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