University of Dundee

Chinese Scholarship Council Programme

CSC - Molecular characterisation of plant disease resistance genes through novel Next-Generation Sequencing applications

This PhD project will provide comprehensive training for the successful candidate in potato genetics (diploid and tetraploid) as well as plant-pathogen genomics/co-evolution. The student will generate and analyse state-of-the-art Next Generation Sequencing (NGS) data for the genetic mapping and the cloning of resistances effective against the late blight pathogen Phytophthora infestans in established segregating populations.

CSC - Exploiting Affinity-directed Protein Missile system to target destruction of misfolded proteins in neurodegeneration

Ubiquitin proteasome system (UPS) controls protein turnover in cells in order to maintain cellular homeostasis (1). E3 ubiquitin ligases facilitate the process of attaching ubiquitin on sustrate proteins. By recruiting E3 ubiqutin ligases to the Proteins of Interest (POIs), we can target specific POIs for UPS-mediated degradation, for example by small molecule proteasome targeting chimeras (PROTACs).

CSC - Decoding gene expression mechanisms in trypanosomes

The African trypanosome, Trypanosoma brucei, is transmitted among mammalian hosts by tsetse flies. These unicellular parasites cause sleeping sickness, also known as Human African Trypanosomiasis, which is typically fatal if left untreated, and the livestock disease known as nagana. Molecular mechanisms underlying antigenic variation and gene expression control remain to be fully characterized.

CSC - Regulation of protein degradation by ubiquitylation

Ubiquitin signalling, which involves the posttranslational modification (PTM) of proteins with ubiquitin, regulates almost every aspect of eukaryotic biology. This versatility is possible because proteins can be modified with different types of ubiquitin codes resulting in distinct functional outcomes. An indispensable role for ubiquitylation is to serve as a signal for the degradation of misfolded and damaged proteins. In addition to degradation, ubiquitin modifications can serve as distinct signals to facilitate intracellular communication.

CSC - Mechanisms of chromosome instability in cancer cells

To maintain genetic integrity, human cells must segregate sister chromatids to opposite spindle poles, prior to their cell division. Errors in this process cause cell death and various human diseases, such as cancers and congenital disorders, which are often characterised by chromosome instability and aneuploidy [1]. Evidence suggests that chromosome instability is closely linked to the aetiology of several types of cancers. Moreover, due to chromosome instability, cancer cells rapidly change their phenotypes, which poses major therapeutic challenges.

CSC - Regulating plant architecture and development through Receptor-like kinase S-acylation

S-acylation is an emerging lipid based post-translational modification affecting up to 40% of membrane proteins. We have found that S-acylation in plants is a dynamic process allowing for regulation of protein function.

We have demonstrated that Receptor-like kinases, the main means by which plants perceive extracellular stimuli such as pathogens, symbiotes, hormones and cell wall status, are regulated by S-acylation.

CSC - Investigating the impact of mRNA cap regulation

We investigate the regulation and function of the mRNA cap, a modification of RNA essential for gene expression which integrates transcript processing and translation.  We are beginning to understand how oncogenes and signalling pathways can regulate gene expression via regulation of mRNA capping enzymes. Signalling pathways which modify the mRNA capping enzymes have the potential to change the gene expression landscape, thus causing changes in cell physiology. 

CSC - Structural and membrane biology of polarized trafficking

Membranes and their protein organization are a frontier in our understanding of cell biology. We focus on polarized trafficking as a model to uncover fundamental mechanisms in the organization of structures at membranes. We aim to understand the role of protein complexes including the exocyst. This project seeks to answer mechanistic questions regarding 1) the regulation of protein structural mechanics in polarized trafficking, 2) and the consequences of signaling on this pathway and its organization.

CSC - Intellectual disability in patients with mutations in O-GlcNAc transferase

Intellectual disability (ID) and associated developmental delay are severe neurodevelopmental conditions that affect approximately 1% of the world population. 5% -10% of ID cases are due to mutations in genes located on the X chromosome. One of the genes shown to co-segregate with X-linked intellectual disability (XLID) in twelve patients is the gene ogt. Ogt encodes an essential enzyme, the O-GlcNAc transferase, which catalyses an abundant nucleocytoplasmic post-transcriptional modification O-GlcNAcylation.

CSC - Chemical Structural Biology and Mechanistic Insights into PROTAC Mode of Action

Pioneering discoveries from the Ciulli Laboratory and others have contributed to the establishment of a new modality of chemical intervention into biological system. The new paradigm-shift concept is that of targeting proteins for degradation using small molecules, as an alternative to conventional target blockade or inhibition. Protein degradation can be undertaken by double-headed molecules, also known as PROTACs, that recruit the target for ubiquitin mediated degradation by complexing them with E3 ubiquitin ligases, notably von Hippel-Lindau (VHL) and Cereblon (CRBN), amongst others.