The aryl hydrocarbon receptor is a ligand-activated transcription factor that acts as a cellular sensor for numerous molecular cues, including environmental, dietary, microbial, disease and drug-related molecules. This key sensor modulates processes highly relevant to cellular, tissue and organism development, maintenance and homeostasis. As a result, its regulation and functions have been connected to diverse immune responses, tissue regeneration and xenobiotic metabolism. It has also been linked to pathological conditions, such as inflammatory disorders and cancer, and modulation of the AHR pathway in response to disruptions in homeostasis can impact therapeutic efficacy.
Investigating the AHR pathway
The potential role of the AHR in both infection and cancer makes it of great interest to the Immune Sensing and Signaling Dynamics group/ImmunoHUB at the i3S. Research technician Sérgio Marinho explained: “The AHR senses the presence of distinct sets of molecules whose expression is affected by various pathological conditions. On recognition of such molecules, the AHR pathway is activated, interacting with diverse signaling pathways – such as TNF-α, NF-κB and MAP kinase – to produce a targeted and tailored response. As it can sense a wide range of ligands, the AHR is used by cells to monitor their microenvironment, providing molecular cues to identify changes in microbial communities or tumor status, as well as allowing the host to react to potential imbalances in homeostasis. Since therapeutic drugs are also recognized by this receptor, the AHR is involved in drug metabolism too, meaning that its modulation could impact the success of therapies, as our group – and others – has demonstrated. We’re investigating this modulation at a fundamental level, to try and understand the effects of infection, particularly where multidrug-resistant bacteria are an issue, and to study why some cancer patients relapse following seemingly successful chemotherapy treatments.”
Making light work of pipetting
The complexity of these types of cell-based investigations means that liquid handling is performed in the laboratory on a daily basis – for both cell culture maintenance and set-up of experiments, including large compound screenings – often for long periods of time. This must not only be accurate and precise, but also ergonomic, to avoid placing unnecessary stress on lab staff. Sérgio continued: “Cell and molecular biology techniques involve a lot of liquid handling. We also perform viral transductions, which require numerous cell handling steps. The PIPETBOY acu 2 pipette controller is ideal for our serological pipetting needs; it is ergonomic, very lightweight, reliable and robust, and compatible with the various serological pipettes that we use in the lab. It also has a long battery life, which is essential when we spend many hours pipetting each day. We use them every day and are very happy with their performance. We also have a VACUSAFE aspiration system from INTEGRA, which is ideal for cell culture assays in microplates. The eight channel tip adapter allows us to aspirate eight wells simultaneously, making the process much less laborious and saving a lot of time. It’s a real asset to our laboratory.”