Dr Zoi Diamantopoulou, Prof Crispin Miller, Prof Colin Semple
Project Description
An exciting PhD position awaits individuals eager to delve into the spatiotemporal regulation of metastasis, the leading cause of cancer related deaths posing a significant hurdle in cancer treatment. Understanding the biology of metastasis and identifying vulnerabilities in the process is imperative for developing novel therapeutic approaches to target and impede metastatic progression.
Our research has uncovered an important role of the circadian rhythm in regulating metastasis. We revealed that the spontaneous generation of Circulating Tumour Cells (CTCs) is not constant throughout the 24-hour day, but instead their numbers exhibit a precise oscillation pattern with the peak observed during the rest phase of the circadian rhythm1. Importantly, CTCs generated during the rest or active phase of the circadian rhythm have different biological properties, with the rest phase CTCs being more prone to form metastases1. Understanding how the circadian rhythm spatiotemporally regulates the tumour microenvironment and affects the generation and metastatic potential of CTCs is crucial for identifying druggable targets that can be exploited to effectively block metastasis.
The development of spatial transcriptomics has revolutionised our understanding of tissue organisation offering a powerful tool to investigate the spatial heterogeneity within tumours2. This technology allows us to unravel the complex interactions between cancer cells with the tumour microenvironment that play a key role in shaping the tumour’s behaviour and metastatic progression. By integrating spatial transcriptomics with other technologies, such as single cell RNA analysis, we can gain a comprehensive insight into the molecular landscape of tumours. However, there is a gap in methods for analysing the spatiotemporal organisation and dynamics of tissues.
Join our collaborative team in developing tools to map the spatiotemporal dynamics of the metastatic tumour. You will also characterise the circadian rhythm-regulated tumour regions responsible for the temporal dynamics of CTC generation and identify vulnerabilities that could serve as potential anti-metastatic targets.
On this project you will gain expertise in metastatic mouse models of colorectal cancer, utilise state-of-the-art microfluidic and robotic devices to isolate CTCs and employ cutting-edge technologies (scRNA analysis, spatial transcriptomics, barcoding). In parallel, you will develop a novel method for aligning spatiotemporal data by extending an existing method for aligning spatial transcriptomics data, Gaussian Process Spatial Alignment (GPSA)3 to include a time component. This research will advance our understanding on metastasis and will pave the way for novel therapeutic interventions.
Training offered
By the end of this project, the PhD student will:
1. Acquire extensive skills in quantitative methods. Specifically, this includes analysing spatial transcriptomics data, multi-modal data and image analysis techniques. With the increasing demands of spatial transcriptomics and deep learning methods for analysis of images, often pre-processing steps need to be run using GPU clusters. As such the student will gain experience in using high performance computer (HPC) environments and deep learning methods.
2. Get expertise in metastatic cancer mouse models and the biology of CTCs.
3. Acquire skills in state-of-the-art microfluidic and robotic devices.
4. Learn how to perform special transcriptomics and scRNA analysis.
5. Communicate effectively in a professional environment through preparation of reports, presentations and manuscripts for publication.
6. Establish a network of collaborators through the network of his/her supervisors and participation in national and international meetings.
7. Develop organisational skills through strategic thinking and planning, prioritisation and time management.
8. Receive scientific integrity training.
For further information on the project or informal enquiries, please contact Dr Zoi Diamantopoulou, This email address is being protected from spambots. You need JavaScript enabled to view it.
To place an application, please visit this site at the University of Glasgow.
When submitting your application please upload the completed recruitment form.
Lab Websites
Dr Zoi Diamantopoulou - Metastasis and Circadian Rythym
Prof Crispin Miller - Computational Biology
Prof Colin Semple - Origins and Impacts of Structural Mutations
Papers of interest
1. Diamantopoulou Z, et al. The metastatic spread of breast cancer accelerates during sleep. Nature. (2022) 607:156-162
2. Rao, A. et al. Exploring tissue architecture using spatial transcriptomics. Nature (2021), 596: 211–220
3. Jones, A. et al. Alignment of spatial genomics data using deep Gaussian processes Nature (2023), 20: 1379–1387
4. Edwards, S.C., et al. PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A–producing γδ Tcells Journal of Experimental Medicine (2023), 220: e20211431
5. ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Pan-cancer analysis of whole genomes. Nature (2020) 578: 82-93