Raff PhD Medal Winner 2024
Saranne Mitchell
Originally from the USA, Saranne followed an unorthodox academic path. While earning her BA in Psychology from the University of Utah, she ran a study on recycling behavior and fell in love 
with research. After graduating, she worked in a biomechanics lab for 5 years, where she published two first author papers on her discoveries of how to maintain epithelial interfaces at bone anchored prosethetics exit sites. As the first person in her family to go to university, this experience gave her confidence to apply for graduate school and join the biomedical engineering program at the University of Utah. Working in Dr. Rosenblatt’s lab she earned her Mphil and relocated with her lab to complete her PhD at King’s College London, UK (photo at Borough Market).
Saranne’s PhD research focused on a highly conserved mechanical mechanism of epithelial cell homeostasis, through elimination, known as extrusion. As the epithelia cells function as a mucosal barrier and are essential to organ function, misregulation of epithelial cell extrusion can lead to tumor formation, or if it is in excess, can lead to inflammation, as seen with asthma. As understanding what regulates extrusion is critical for preventing a growing number of diseases, Saranne’s main work focused on how individual crowded cells are selected for extrusion. She discovered found that low cellular energy mechanically triggers water-based cell shrinkage that induces most crowding-cell extrusions (schematic). Additionally, she independently initiated a project investigating how the membrane anchored mucus that covers most organ epithelial membranes impacts extrusion. Here, she found that this sugary coating can suppress extrusion. Dampening extrusion could be protective in cases where there is excess extrusion but could also contribute to diseases like lung fibrosis.
Her main discovery stemmed from a surprising finding that cells transiently shrink before they extrude using standard phase microscopy. Early cell shrinkage was upstream myosin contraction and all other previously known extrusion signals. Instead, transient water loss via activation of the voltage-gated potassium channels Kv1.1 and Kv1.2, and chloride channel SWELL1 causes the brief shrinkage. Since these potassium channels are voltage-gated, 
it suggested that an electrical current might initiate extrusion. Imaging membrane depolarization with the dye DiBAC4(3) indicated that indeed cells lose membrane potential before extruding and that activation of the tension-sensitive Epithelial Sodium Channel is essential for this loss. As most of the energy in a cell is used to maintain a membrane potential, this suggests that crowded cells with insufficient energy are selected for extrusion. The crowding probes for cells with weak energy, which then mechanically shrink by inducing a brief voltage-gated-dependent water loss, which then kicks off the extrusion and their elimination from the monolayer to retain the most energy-fit cells. This study (https://www.biorxiv.org/content/10.1101/2023.03.13.532421v1) is under revision.
In addition to working in the lab, Saranne is passionate about inspiring and fostering women in science. She has organized an annual outreach program called “women in science scholar day” at King’s College London. For this project, she actively recruits women with diverse science backgrounds including physics, biology, and biomechanics to give them an integrative learning experience. Additionally, she has mentored many female undergraduates, the most recent of whom did so well, she has joined the lab as a PhD.
You can follow Saranne on LinkedIn.
Saranne will be awarded the Raff Medal and give a talk about her research during the 90th Harden Conference joint BSCB/Biochemical Society co-organised meeting cell migration meeting which will be held on 15-18 April 2024 at Birmingham, UK.
The BSCB PhD Award – Raff Medal was established in 2020 to recognise BSCB PhD students who have made outstanding contributions to UK/Ireland cell biology. The medal has been named after Professor Martin Raff who was the president of BSCB from 1992-1995. Martin was instrumental in setting up and running the first 4-year PhD graduate programme in Molecular Cell Biology at the MRC Laboratory for Molecular Cell Biology (LMCB) at UCL.