Recent Doctoral Graduates from the Kavli Institute for Nanoscience Discovery: Dr Christy Sadler and Dr Johanna Hoffmann
Dr Christy Sadler
Thesis title: Engineering the Bio-Nano Interface for Enhanced Biosensing Applications
Supervisors: Professor Dame Molly Stevens
Thesis summary: Rapid and low-cost diagnostic tests play a critical role in the diagnosis and surveillance of disease, yet many tests require centralised facilities and trained personnel to operate. There is a global drive toward the implementation of point-of-need testing programmes, such as the paper-based lateral flow assays (LFAs) used for COVID-19 surveillance. However, LFAs often exhibit performance-based shortcomings compared to traditional diagnostic tests, including poor stability, sensitivity and robustness. During my DPhil, I investigated approaches to address these shortcomings to improve the performance of LFAs, through the engineering of test components to manipulate functionality.
My research focused on addressing key shortcomings of LFA performance and development, including stability, analytical sensitivity, and robustness:
Stability: Traditionally, antibodies are used as biorecognition elements in LFAs to recognise and bind to the disease-specific target. However, antibodies often demonstrate poor stability under elevated temperatures and humidity levels. We investigated how affibodies (a class of alternative affinity proteins) could be integrated into traditional LFA architecture to improve assay stability, while maintaining industry-standard manufacturing processes.
Analytical sensitivity: Reducing the detection limit enables the early identification of disease, aiding disease control and accelerating access to appropriate treatment. We developed a strategy to reduce the detection limit through the coupling of nanoparticles, which are employed to generate a visually detectable signal. This approach increases the number of nanoparticles immobilised in the test region to increase the signal that can be detected.
Robustness: Biological samples (such as plasma, serum and saliva) are intrinsically complex, containing an array of proteins, lipids, and small molecules; the concentrations of these components can vary significantly between patients. The nanoparticles employed in LFAs can interact with components of the biological sample, leading to changes in nanoparticle stability and targeting ability. We investigated how the interface between nanoparticles and human serum could be engineered to reduce the observed inter-patient LFA performance variability.
Next steps: After completing my DPhil and a short postdoctoral researcher position within the Stevens group, I have recently started a role as Program Lead at a new life sciences startup. The company is currently operating in stealth, and I am excited to share more about the startup as it grows!
Insights on interdisciplinarity: Throughout my DPhil, I have been directly involved in several cross-disciplinary collaborations, both within the University and internationally, which have shaped my research. My time in the Stevens group and the Kavli Institute demonstrated that fostering an interdisciplinary environment is crucial to a bridging the gap between fundamental science and translational research.
Dr Johanna Hoffmann
Thesis title: Understanding Intracellular Calcium Dynamics in Human Parkinson’s Patient Stem Cell Neurons
Supervisors: Professor Richard Wade-Martins, Professor Stephanie Cragg, Dr Maria Claudia Caiazza
Thesis summary: Parkinson’s disease (PD) is a neurodegenerative disorder characterised by the progressive loss of dopamine-producing neurons. Increasing evidence points to dysfunction of the lysosome – the cell’s recycling system – as a key contributor to disease development. My DPhil research focused on understanding how intracellular calcium (Ca²⁺) signalling, particularly within lysosomes, contributes to this dysfunction.
Using human induced pluripotent stem cell (iPSC)-derived dopamine neurons from PD patients carrying either a GBA1 mutation or SNCA triplication, I investigated how disease-associated mutations affect lysosomal calcium dynamics and downstream cellular function. By combining direct measurements of lysosomal Ca²⁺ with functional assays of lysosomal degradation, I assessed how these changes impact the ability of cells to process and recycle material.
I identified alterations in lysosomal Ca²⁺ homeostasis accompanied by impaired degradative capacity, changes in lysosomal pH, and reduced enzyme activity. Notably, genetic reduction of a key lysosomal Ca²⁺ channel was sufficient to reproduce similar lysosomal phenotypes, supporting a central role for this pathway in maintaining lysosomal function.
More broadly, this work highlights the importance of intracellular ion regulation in maintaining neuronal health. By improving our understanding of how lysosomal signalling is disrupted in PD, these findings contribute to ongoing efforts to identify pathways that could be targeted to restore cellular function in neurodegenerative disease.
Next steps: I have recently started a postdoctoral position at the RIKEN Institute in Wako, Japan, in the Laboratory for Molecular Pathology of Psychiatric Disorders. Over the course of a one-year fellowship, I will continue working on neurodegenerative disease, this time focusing on RNA sequencing and computational analysis to gain a transcriptomic perspective on disease-relevant pathways.
Insights on interdisciplinarity: This project combined imaging and functional approaches in human disease-relevant models, reflecting the integrative nature of neurodegeneration research. The diverse expertise within the Kavli Institute of Nanoscience Discovery provided a valuable broader context and additional perspectives, including through a collaborative small molecule project. I think bringing together different approaches and areas of expertise will be increasingly important for advancing our understanding of complex diseases.
