Past ECR Seminar Speakers

Octobers 2026 speakers:

Charlene Dambire from the University of Nottingham, who presented:

"Activated by cleavage: Protease-driven protein regulation in plant responses to environmental cues"

Natalia Jimenez Moreno from Simon Wilkinson's lab at the University of Edinburgh who presented:

"Beyond ER-phagy: a condensate-nucleated degradative hub sequestering FAM134B and RhoA to govern cell morphology"

A Bit About Charlene :

Dr Charlene Kunaka-Dambire is a BBSRC Discovery Research Fellow in the School of Biosciences at the University of Nottingham, where she leads research investigating how plants sense and respond to environmental stress. Her research focuses on protease biology, protein stability and the N-degron pathways, with particular interest in how targeted protein degradation regulates plant adaptation to changing environments.

Charlene has contributed to significant advances in understanding the roles of substrates of the oxygen-sensing PCO N-degron pathway, a molecular system that enables plants to respond to changes in oxygen availability. Her research has contributed to publications in leading journals, including Nature Communications (2018;2023;2026) and Nature (2022).

As a BBSRC Discovery Research Fellow, Charlene is developing an independent research programme investigating the role of protease-triggered protein function in the model plant species Arabidopsis thaliana, with the broader aim of uncovering mechanisms that enhance our understanding of plant stress resilience and their potential relevance to sustainable agriculture and food security.

Originally from Zimbabwe, Charlene is also passionate about mentorship in STEM for women and girls. She received the 2025 UK Black in Plant Science Research Excellence Award in recognition of her scientific contributions and advocacy and supporting the empowerment of girls to pursue opportunities and careers in STEM.

Talk Title:

"Activated by cleavage: Protease-driven protein regulation in plant responses to environmental cues"

Abstract for her Talk:

Intracellular proteolysis is traditionally viewed as a destructive process that eliminates proteins through proteasomal degradation. Our work challenges this paradigm by asking: why are proteins cleaved at specific sites if their fate is ‘just’ degradation? We demonstrate that selective proteolytic cleavage of proteins can generate functionally distinct protein fragments (proteoforms) whose stability and activity are conditionally regulated by the N-degron pathways, thereby rewiring plant responses to environmental cues.

The N-degron pathways target proteins for proteasomal destruction based on their exposed N-terminal amino acid following cleavage of proteins by proteases, providing a mechanism to determine the fate of proteoforms.
We showed in model plant species, Arabidopsis thaliana that the protease METHIONINE AMINOPEPTIDASE removes the initiating methionine from ERFVII transcription factors, exposing an N-terminal cysteine that is oxidised by PLANT CYSTEINE OXIDASES (PCOs), resulting in arginylation by ARGINYL TRANSFERASES (ATEs), and recognition by the E3 ligase PRT6, leading to proteasomal degradation. Our work revealed that under hypoxia, inhibition of PCO activity stabilises ERFVIIs, enabling activation of hypoxia-responsive genes and promoting adaptation to low oxygen and high-altitude environments.

Extending this principle, we identified the protease METACASPASE9 (MC9) as a regulator of multiple substrates whose cleavage products are controlled by the ATE N-degron pathway. MC9 cleavage of the transcription factor HY5 generates E59-HY5, a proteoform that escapes COP1/SPA-mediated degradation and acts as a fail-safe developmental regulator during photomorphogenesis, while also controlling the unfolded protein response. We also show that MC9 similarly cleaves the proteasome-associated deubiquitylase UBIQUITIN PROTEASE6 (UBP6), producing the E157-UBP6 proteoform, whose stability and function is likewise regulated by the ATE N-degron pathway following pathogen perception.

Together, our findings reveal how plants couple proteolysis with N-degron pathways mediated conditional stability to dynamically coordinate their responses to environmental cues, demonstrating that proteolytic cleavage can generate new regulatory states rather than simply marking proteins for destruction.

A Bit About Natalia:

I am a cell biologist specializing in autophagy—the cellular "self-eating" degradation process responsible for clearing damaged components to maintain health and homeostasis. I earned my B.Sc. in Biochemistry (2014) and M.Sc. in Molecular Biology (2015) from the Autonomous University of Madrid, followed by a Ph.D. in Dynamic Cell Biology (2020) at the University of Bristol through the Wellcome Trust program under Prof. Jon Lane’s supervision. Currently, I work as a Postdoctoral Researcher at the University of Edinburgh's Institute of Genetics and Cancer within Prof. Simon Wilkinson’s lab. My research investigates the molecular mechanisms of ER-phagy (the selective autophagy of the endoplasmic reticulum), uncovering new pathway components and exploring their physiological roles in protein homeostasis and oncogenesis. Outside of my core research, my primary focus right now is writing fellowship grants to secure my independence—which takes up most of my time! Whenever I do have free time, I love spending it with my 7-year-old daughter, Selena.

Talk Title:

"Beyond ER-phagy: a condensate-nucleated degradative hub sequestering FAM134B and RhoA to govern cell morphology"

Abstract for her Talk:

The endoplasmic reticulum (ER) is a dynamic organelle that undergoes continuous remodelling via a selective form of autophagy known as ER-phagy. ER-phagy receptors such as FAM134B/C are canonically defined as cargo adaptors that cluster with the autophagosomal protein LC3B to drive ER remodelling; however, their broader physiological functions and regulatory mechanisms remain elusive. Using proximity proteomics in pancreatic cancer cells, we identify PRKAR1A — a regulatory subunit of PKA — as a direct, cAMP-responsive binding partner of FAM134B/C, acting independently of PKA catalytic subunit inhibition. FAM134B engages PRKAR1A dimers via an amphipathic helix within its disordered C-terminus, docking into a hydrophobic pocket in the PRKAR1A dimerization domain.

Using SoRA super-resolution imaging, FRAP, and CLEM, we show that cAMP-bound PRKAR1A forms liquid-like condensates that establish direct contacts with the ER membrane. At these contacts, PRKAR1A actively clusters ER-embedded FAM134B/C with LC3B and recruits lysosomes locally, scaffolding a spatially discrete degradative hub for turnover of the receptor.

Critically, beyond ER cargo, this hub also sequesters the cytoskeletal GTPase RhoA, driving its co-degradation alongside FAM134B/C. Underscoring the physiological relevance of this, these cytoplasmic-facing actions of FAM134B/C control actomyosin contractility and ultimately dictates cell morphology and cancer cell invasion modality.

In summary, we describe a novel inter-organellar contact between liquid condensates and the ER that serves as a cellular degradation hub. These hubs coordinate ER remodelling with cytoskeletal dynamics, broadening the role of ER-phagy receptors beyond homeostatic maintenance to the active regulation of cellular morphology and cancer metastasis.

September 2026 speakers:

Mary Tozer from Doreen Cantrell's lab (University of Dundee), who presented:

"Glucose Availability Controls Selective Protein Turnover in Effector CD8 T Cells"

and

Katherine Fenn from the lab of Neil Ranson/Sheena Radford (University of Leeds) who presented:

"BAM-BepA complexes in outer membrane protein quality control"

A Bit About Mary:

Mary is originally from London and currently based at the University of Dundee, Scotland. She has recently submitted her PhD thesis supervised by Prof. Doreen Cantrell. The Cantrell lab works on T lymphocytes, which are key mediators of anti-viral and anti-tumour immune responses. Mary uses proteomics, complemented by wet lab techniques, to study how CD8 cytotoxic T lymphocytes respond to extracellular signals like cytokines and exogenous glucose to selectively control proteome stability and protein turnover. As part of this research, she has mapped the half-lives of over 6,000 proteins in cytotoxic T cells. Outside the lab, Mary enjoys music festivals and meandering around museums, and can be found at Parkrun every Saturday morning, rain or shine.

Talk Title:

"Glucose availability controls selective protein turnover in effector CD8 T cells"

Abstract for her Talk:

Glucose-sensing pathways in CD8 T cells respond to glucose depletion by modulating kinase signalling networks and protein stability to shape cell fate. High resolution mass spectrometry reveals that glucose availability controls effector CD8 T cell proteostasis, whereby withdrawal of exogenous glucose leads to a marked loss in abundance of cytokine receptors and proteins that control cell cycle progression, survival and cholesterol homeostasis; whilst driving increased abundance of the protein translation repressor PDCD4. We identify that protein synthesis is partially glucose-dependent in effector CD8 T cells, representing a key node through which glucose availability controls proteostasis. We further map protein half-lives for over 6,000 proteins, showcasing the remarkable dynamism and selectivity of protein renewal in effector CD8 T cells, which turn over more than 500 proteins every 3 hours. Notably, cytokine receptors were strongly represented amongst short half-life proteins. These data are key to understanding how any factor impacting protein synthesis will lead to loss of short half-life proteins, and indeed the ability of effector CD8 T cells to respond to cytokine signals at the site of immune activity.

A Bit About Katherine:

Katherine Fenn is a postdoctoral researcher at the University of Leeds. Her work focuses on understanding the delivery and misdelivery of OMPs to the bacterial OM. She received her PhD in Biological Sciences (2021) from Queen Mary University of London on membrane proteins involved in pathogenesis and their host-cell interactions.

Talk Title:

"BAM-BepA complexes in outer membrane protein quality control"

Abstract for her Talk:

Correct folding of outer membrane proteins (OMPs) by the β-barrel assembly machinery (BAM) is essential for maintaining the outer membrane (OM) barrier function of diderm bacteria. When OMP biogenesis is perturbed, the β-barrel assembly enhancing protease A (BepA) binds to BAM to mediate quality control, but how BepA interacts with BAM and degrades substrate OMPs remains unclear. Here, cryoEM structures of BAM-bound BepA reveals that BepA induces large conformational changes in the BAM complex enabling the enzyme to poise its active site within the periplasmic ring of BAM, beneath the BamA barrel. The lid of BepA is dynamic, embedding two of its water-soluble helices deep into the membrane bilayer when BAM-bound, which readies BepA for proteolysis of misfolding OMPs. Movement of BepA’s plug is triggered by OMP binding rather than interaction with BAM, activating the enzyme for cleavage. We reveal BepA preferentially recognises Aromatic-X-Aromatic (Ar-X-Ar) motifs which are enriched in OMP sequences. The results reveal a mechanism for proteolytic degradation by BepA in OMP quality control which requires interaction with BAM, the membrane, and its OMP substrates.