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 If you are a potential supervisor, [[supervisor_instructions:click here]]
+=== Investigation of the effect of the circadian rhythm on the genetic control of gene expression ===
+Contact: Sonia shah <sonia.shah@imb.uq.edu.au>, Solal Chauquet <uqschauq@uq.edu.au >
+The circadian rhythm reflects the daily cycle of behaviours and metabolic processes organisms exhibit. A 24-hour gene expression pattern occurs at the molecular level, with genes activated either during the day or night. Different tissues all display circadian control, with some more affected than others. Within the liver, for example, 3000 genes are subjected to circadian control. This regulation is orchestrated by a small group of CLOCK genes, establishing feedback loops that result in rhythmic gene expression in every tissue.
+We know that gene expression can be influences by genetics variants, called expression quantitative trait loci (eQTL), and this may be one mechanism linking genetic variants to disease. As a result, large eQTL datasets have been generated to assist in understanding disease mechanisms. However, it remains unknown whether sample collection time can affect eQTL identification. This project therefore aims to identify the possible effects of the circadian rhythm on the genetic control of gene expression using the Genotype-Tissue expression (GTEx) dataset.
+During this project, you will run Python tools such as PEER and tensorQTL to identify eQTL within 49 tissues. You will subsequently investigate the associations identified and follow up on the role of the genes under circadian controls within different phenotypes.
+=== Understanding the influence of taste and olfactory perception on eating behaviour and health conditions using big genetic data ===
+Contact info: Daniel Hwang <d.hwang@uq.edu.au>
+Project description: Human perception of taste and smell plays a key role in food preferences and choices. There is a large and growing body of work suggesting that taste and smell (together known as "chemosensory perception") determine eating behaviour and dietary intake, a primary risk factor of chronic conditions such as obesity, cardiometabolic disorders, and cancer. Evidence to date is largely based on observational studies that are susceptible to confounding and reverse causation, leaving the "causal effects" of chemosensory perception on food consumption unclear. If their relationship is truly causal, flavour modification may represent a tangible way of modifying food consumption in a way that benefits public health outcomes. This project aims to: (i) elucidate the genetic architecture underlying individual differences in taste and smell perception, (ii) use this information to assess their causal effects on eating behaviour, and (iii) create a sensory-food causal network mapping individual sensory qualities (i.e. sweet taste, bitter taste, and more) to individual food items.
+=== Increasing drug success rate in human clinical trials using genomics ===
+Around 90% of drug candidates fail in human clinical trials largely due to lack of efficacy or safety concerns. This partly reflects the limitations of using in vitro and animal studies to predict the effect of compounds in humans. Recent studies highlight that drug targets backed by evidence from human genetic studies are 2 times more likely to make it to market. Human genetic data can also identify potential adverse side effects. Such information prior to embarking on human clinical trials could improve the success rate of a compound in human clinical trials and help avoid adverse outcomes for participants. This project will use statistical genomics analyses using publicly available human genomic data to predict efficacy as well as any safety concerns of compounds that are currently in the drug development pipeline.
+Project significance: Findings from this project could potentially identify new therapeutic applications for these compounds or unknown side effects, and ultimately informing future human clinical trials.
+Contact: Sonia Shah <sonia.shah@imb.uq.edu.au>
+Supervisors: You will be working with a multidisciplinary team of supervisors Prof Dave Evans, Dr Sonia Shah, Prof Glenn King, Assoc/Prof Nathan Palpant
+Familiarity with computational analyses (e.g using R or python etc) is needed for this project. Some knowledge around genome-wide association studies and statistical genomics methods such as Mendelian randomisation analysis would be beneficial
+=== Developing quiescent stem cell classifier using single cell transcriptomics ===
+Contact info: Dr Lachlan Harris (Lachlan.Harris@qimrberghofer.edu.au), Dr Olga Kondrashova (Olga.Kondrashova@qimrberghofer.edu.au)
+Quiescence is a reversible state of cell-cycle arrest, sometimes referred to as the “G0” phase of the cell-cycle. It is an adaptive feature of most adult stem cell populations, where it ensures that stem cells divide only when needed, preserving regenerative capacity. However, quiescence is also adopted by cancer stem cells to evade chemo- and radiotherapies that preferentially kill fast-dividing cells. Single-cell data promises to uncover the molecular regulation of quiescent stem cells in health and disease but the identification of these cells within these datasets is either reliant on expert knowledge and manual curation or is currently impossible, due to a lack of marker genes.
+The most common classifiers that define cell-cycle stages (G1/S/G2/M) in single-cell RNA-sequencing data (scRNA- seq) were trained on populations of actively cycling cells. Therefore, these tools cannot identify quiescent stem cells in “G0” phase of the cell-cycle. It is an outstanding question as to whether there are sufficient transcriptomic similarities across quiescent stem cells from different tissue types to build a generalisable model to discriminate these cellular populations. Furthermore, it is unknown whether such a model would generalise to cancerous tissue, where increased variability in transcriptomic states often degrades the distinction between cell types.
+This project aims to develop a broadly applicable quiescent classifier. As a first step towards this, this project will seek to 1) contribute to the curation of datasets and isolation of tissue-agnostic and tissue-specific feature sets that define quiescent stem cells and 2) compare methods for training quiescent classifiers and for determining the most salient features.
+=== Understanding sex-specific cardiovascular disease risk ===
+Contact info: Dr Sonia Shah (sonia.shah@imb.uq.edu.au), Dr Clara Jiang (j.jiang@uq.edu.au)
+Description: Cardiovascular diseases (CVD) account for 35% of female deaths globally (29% in Australia). However, CVDs remain under-studied, under-diagnosed and under-treated in women. This sex disparity is partly due to the lack of knowledge of female-specific risk factors. This project involves statistical analysis of large-scale health and genetic data to identify sex-specific CVD risk factors and underlying mechanisms.
+Requirements: A background in genetics and computational data analysis is preferable.
 === De-risking the drug development pipeline by finding biomarkers of drug action ===
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 The project is embedded in the [[https://imb.uq.edu.au/research-groups/nefzger|Nefzger lab with a major focus on “Cellular reprogramming and Ageing”]]. The applicant will be closely working with [[https://imb.uq.edu.au/profile/11267/marina-naval-sanchez|Dr. Naval-Sanchez]]  as the main supervisor.
+=== Decoding Transcription Factor Dosage Effects on Cell State Transitions with DoseH-Seq ===
+Contact info: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au), Ralph Patrick (ralph.patrick@imb.uq.edu.au) and Marina Naval-Sanchez (m.navalsanchez@imb.uq.edu.au)
+Cell identity is controlled by different combinations of transcription factors (TFs) that bind to genomic regulatory elements to regulate gene expression. TF activity is not binary in most instances but graded and in response to TF dosage levels (e.g., Naqvi et al., Nat Genet., 2023, PMID: 37024583). For this reason, TFs are strongly enriched for haploinsufficient disease associations (Seidman et al, 2002, J. Clin. Invest. PMID: 11854316; Van de Lee et al., 2020, Trends Genet., PMID: 32451166) and TF dosage and stoichiometry strongly affects reprogramming outcomes (e.g., Polo et al, 2012, Cell, PMID: 32939092; An et al., 2019, Cell Reports, PMID: 31722212). Furthermore, TF dosage effects may also underlie seemingly contradictory effects linked to overactivation of certain TFs in cancer contexts, including of the Nfi family (Becker-Santos, 2017, The Lancet Discovery Science, PMID: 28596133).
+Single-cell RNA+ATAC-seq is a uniquely powerful assay to measure the impact of TF levels on cell regulatory architecture; however, no tools currently exist to directly study TF dosage effects on temporal cell state transitions. To address these gaps, we developed Dosage and Hashtag sequencing (DoseH-seq), an expansion of the 10x Genomics single-nucleus (sn)RNA+ATAC-seq assay that enables sensitive detection of lentiviral perturbations (e.g., TFs) linked to a heterogeneously expressed promoter. In combination with sample hash tagging, multiple temporal, and dosage states, for theoretically any number of genes of interest, can be profiled. This allows detection of TF dosage-dependent effects on temporal cell state transitions, chromatin architecture, co-factor expression, and the rewiring of TF networks at high-resolution. Compatibility with BGI sequencing technology enables the generation of low-cost datasets.We demonstrate the utility of DoseH-seq by tracking the dosage effects of somatic transcription factor, Nfix, during reprogramming towards pluripotency. Contrary to the current dogma, we find that Nfi overexpression can act either as a reprogramming roadblock or as a reprogramming booster, depending on TF dosage and context. These insights may help resolve the TF’s paradoxical role in cancer. DoseH-seq represents a powerful tool for elucidating, and ultimately controlling, both desired and pathological cell state transitions.
+The applicant would help drive method establishment around our novel DoseH-seq technique and support analysis to understand TFs dosage effects with established data sets. Ideal candidate will be able to efficiently program in R or Python. This project is looking for bioinformatics Masters students (ideally 16 units, but we consider 8 unit applicants as well. We also consider PhD students.