Dr Ye Dee Tay

(he/him)

D.Phil. FHEA

Publication

• Date
• Type

Research

Cell polarity regulation by Cdc42 GTPase (University of Edinburgh)

Cdc42 GTPase is a pivotal enzyme in eukaryotic cells. Cdc42 is essential for establishing and maintaining cell polarity, a critical aspect for various cellular processes including migration, differentiation, and tissue organization. Using fission yeast as a model organism, I explored the intricate mechanisms by which microtubules and various interactors of Cdc42 orchestrate the spatial organization of active Cdc42 clusters within cells. This research not only elucidates the fundamental role of Cdc42 in cell polarity but also contributes to our understanding of how cytoskeletal dynamics and signalling pathways integrate to control cellular architecture and function.

Active Cdc42 clusters in fission yeast are depolarised upon stress

Regulation of exocytosis by Orb6 kinase via phosphorylation (University of Edinburgh)

Orb6 kinase in fission yeast is a member of the LATS kinase family, which, in mammalian cells, plays a crucial role in regulating cell proliferation, growth, apoptosis, tumour suppression, and cell polarity. Using a systematic mass spectrometry-based approach, I identified a substantial number of potential substrates of Orb6 kinase. My research revealed that Orb6 kinase regulates the exocytosis process through phosphorylation of the key enzyme complex known as the Exocyst. This finding highlights the conserved function of LATS kinases across eukaryotic species and underscores the importance of Orb6 in maintaining cellular processes by controlling vesicle trafficking and membrane fusion.

Cell cycle control through phospho-regulation of Wee1 kinase (University of Manchester)

Wee1 kinase is a crucial enzyme that regulates Cdc2 (also known as CDK1), the master regulator of the cell cycle in eukaryotic cells. I genetically engineered a fission yeast Wee1 kinase that can be precisely “switched on or off” in vivo using a small chemical inhibitor, enabling the selective activation or inhibition of Wee1 function. This innovative approach allowed me to dissect the role of Wee1 kinase in real-time within living cells. Additionally, I investigated the post-translational modifications of Wee1 kinase throughout the cell cycle. My research provided insights into how these modifications influence Wee1 activity and stability, thereby ensuring proper timing of cell cycle transitions and maintaining genomic integrity. These findings contribute to a deeper understanding of the regulatory mechanisms governing cell cycle progression and have potential implications for developing targeted therapies in cell cycle-related diseases.

Fission yeasts carry out nuclear division (mitosis) synchronously upon Wee1 kinase inactivation

Investigation of DNA double-strand break repair mechanism using yeast genetics (University of Oxford)

The Holliday Junction (HJ) is a crucial DNA intermediate that physically connects two stretches of homologous DNA, forming during the latter stages of homologous recombination. This process is essential for repairing DNA double-strand breaks and maintaining genome stability. At the time of my study, the specific enzymes responsible for the resolution (cutting) of HJs in eukaryotic cells were unknown. To address this, I constructed a plasmid-based artificial HJ molecule, which served as a tool for screening potential HJ-resolving enzymes. This innovative approach aimed to identify and characterize the enzymes involved in this critical repair pathway. In addition, I explored the link between the gene Mph1 (mutator phenotype I) and the DNA mismatch repair pathway, using budding yeast model. My research provided new insights into the interplay between different DNA repair mechanisms and contributed to our understanding of how cells maintain genomic integrity through accurate DNA repair processes.

Teaching

• Eukaryotic Cell Structure
• Genetic Interaction and Mutation
• Cell & Tissue Structure
• Extracellular Matrix
• Advance Cell Biology and Imaging

Biography

I grew up in Tawau, a small town on Borneo Island in East Malaysia, where I developed a deep interest in science, particularly biology. I came to the UK to study BSc in Biomedical Sciences in the University of Hull, who sponsored my study through Lord Wilberforce Full Scholarship for international student. Inspired by my final-year research project, I decided to pursue a career in research and was subsequently awarded a Clarendon Scholarship and Cancer Research UK PhD Studentship to study Medical Oncology at the University of Oxford. This transformative experience introduced me to the fascinating world of molecular and cellular biology and basic sciences research.

After my PhD, I conducted post-doctoral research at the CRUK Manchester Institute (formerly Paterson Institute) with Prof. Iain Hagan, focusing on cell cycle studies in fission yeast. I then continued my research at the Wellcome Trust Centre for Cell Biology at the University of Edinburgh with Prof. Ken Sawin and Prof. Andrew Goryachev, investigating Cdc42 GTPase-mediated cell polarity.

Throughout my academic journey, I have had the privilege of supervising numerous undergraduate and postgraduate students, which has fuelled my passion for teaching in higher education. During the COVID-19 pandemic, when research activities slowed down, I seized the opportunity to complete a Postgraduate Certificate in Academic Practice (PgCAP) and received a secondment for teaching undergraduate biological sciences at the University of Edinburgh. This teaching experience cemented my enthusiasm for teaching, leading me to join Cardiff University in 2023 as a full-time lecturer in Biomedical Sciences. My commitment to the scholarship of teaching and learning drives me to continually seek innovative ways to enhance the educational experience for my students, and engage with UK and global higher education teaching communities.

Honours and awards

• Fellow of Higher Education Academy

Professional memberships

• Member of British Society for Cell Biology
• Member of Biochemical Society