Magnetic fields are ubiquitous in the interstellar medium but their detailed role in the formation of stars is as yet unclear. In the dense star forming regions of molecular clouds the magnetic field can be traced through observations of the polarized continuum emission from dust grains which align with the magnetic field. However, to understand how magnetic fields affect the evolution of the gas, observations of the magnetic field must be combined with observations of the cold, molecular gas in the regions. This project will study the impact of the magnetic fields as gas flows from parcsec-scale clumps down to individual star forming cores and protostars. It will involve observations of polarization emission from dust and molecular lines to study the magnetic field and molecular gas covering a wide range of size scales in star forming regions. Part of the project will be developing new methods to compare the polarization and line observations with the results of state-of-the-art magneto-hydrodynamics simulations.

This project will create de novo enzymes for efficient and selective conversion of CO2 into CO and commodity chemicals, building from a first generation de novo CO2 reductase enzymes developed in the PI lab. Characterization of these de novo enzymes will provide a detailed understanding of the active site features and catalytic mechanisms controlling CO2 reduction and transformation to underpin the design of future generations of catalysts. These ambitions will be achieved by employing state-of-the-art methods in computational enzyme design, structural biology, genetic code expansion, directed evolution and biophysical enzyme characterization.

The brain's vasculature is highly specialised. It tightly regulates transfer of essential molecules and ions into the brain, constantly maintaining a carefully balanced extracellular milieu in which neurones and other brain cells can function properly. In many neurological diseases such as dementia, stroke and brain tumours, the brain's vasculature becomes dysfunctional, allowing molecules to enter the brain unimpeded, disrupting this tightly controlled neurochemical balance. The transfer rate of water into and out of the brain is a common factor affected by disease. The correct regulation of water movement between different compartments of the brain is important for several reasons: i) Even small changes in the distribution of water between cellular compartments can drastically affect the composition of extracellular fluid, and hence the ability of brain cells to function properly, ii) Effective clearance and circulation of water in the brain is essential for removal of waste products such as amyloid-B, a protein which accumulates in brain's of people with Alzheimer's disease. The importance of well-regulated water balance is becoming increasingly recognised. There is now a need to understand the biophysical factors that drive changes in vascular water exchange so that drugs can be developed to restore brain water homeostasis. Our lab has developed approaches to measure vascular water exchange using MRI and we have demonstrated these method can detect changes in water exchange associated with ageing, AD, and peripheral inflammation. We now wish to use these techniques to study how changes to vascular proteins such tight junctions and aquaporins impact brain water balance, and how these changes impact brain health. This project will involve the use of knock out mouse models to determine the impact of specific genes on vascular and perivascular water exchange, then investigate the impact of abnormal water transport/movement in mouse models of Alzheimer's disease.

The information for life is encoded in the DNA of the genes harboured in our chromosomes. The DNA in a chromosome is a very long chain consisting of four different nucleotides: G, A, C and T. For most genes this code is then converted into a messenger RNA intermediate (mRNA) that has a cap structure and a polyA tail to protect it from degradation. This mRNA is then translated in the cytoplasm into a chain of amino acids called proteins, which fulfil a function; for example an enzymatic reaction to generate energy from the nutrients we eat to allow for the electrical communication among neurons in our brain. Although the sequence of mRNA only consist of four nucleotides, many can be modified by addition of small chemical groups to increase the regulatory portfolio and coding capacity. The most prominent modification in mRNA are methyl groups added to the nucleotides adjacent to the cap structure. Animals including humans have two cap methyltransferase enzymes (CMTrs) that add these modifications. Also many parasites have a CMTr gene in their genome that is required for their propagation. In mice, CMTrs are essential and required for neuronal development, however, the biological functions of CMTrs and the mRNA cap modifications remain largely unexplained. We recently discovered that mutant Drosophila lacking both CMTrs are viable, although they suffer from neurological and learning defects. Intriguingly, we further discovered that in these mutant flies, mRNAs were not properly transported to synapses, which are the sites where signals are transmitted to neighbouring neurons. In particular, we could show that some mRNAs are only made into protein at synapses. Hence, the cap modifications have an essential role in directing the synthesis of new proteins locally at synapses suggesting that this process is required for learning of new associations, that are then stored as memory in the brain. However, we currently do not know which genes are expressed in this way at synapses nor what the sequence code is to direct mRNAs to synapses for localized expression. We now have the ideal animal model to address the very fundamental questions about how this enigmatic modifications direct local expression of genes to synapses. Our preliminary data indicate that the cap modifications vary between different animals and conditions. Since CMTrs also localize to synapses, our data suggest a dynamic code important for local protein synthesis. In a first step to crack this code, we will identify specific mRNAs that localize to synapses allowing us to build a reporter system to test the code. To complement this analysis we will further determine the sequence preferences of CMTrs in biochemical assays and identify proteins important for CMTr specificity and decoding of the cap modification code. These studies are essential to understand the vital function of the cap modifications in the regulation of gene expression and how its aberrant regulation can lead to neurological defects in humans, or can be exploited to interfere with viral replication such as in SARS-CoV-2.

Overview of the research This PhD research will examine, through an interdisciplinary crime science and security studies perspective, how factors of systemic corruption facilitate illicit financial flows, such as money laundering and sanctions busting, during the early post-Cullen Commission era in Canada (Cullen, 2022). Within this framework, the project will conduct an end-to-end crime script and network analysis of cyber-enabled financial fraud schemes, such as "pig butchering" - a type of crypto investment social engineering-cum-romance scam (Cross, 2023; Kassem and Carter, 2023). Pig butchering scam operations are sophisticated, long term, all-in-one crypto asset securities fraud schemes perpetrated by transnational organised crime groups and hostile nation state-sponsored enterprises that have adopted mass telemarketing and platform-as-a-service business models. These schemes rely on professional enablers found within multiple sectors such as third-party corporate services, money services businesses, crypto trading platforms, and web hosting providers of all degrees of knowingness and complicity to commit their illicit activities offshore and multi-jurisdictionally (ACAMS and Homeland Security Investigations, 2022; US Immigration and Customs Enforcement, 2023; Basel Institute on Governance and EUROPOL, 2022). This criminal industry is known to exploit human trafficking and money laundering networks often orchestrated within Special Economic Zones across ASEAN countries and leverage guanxi of the global Chinese diaspora to build and violate digital trust (McPherson and Wilson, 2023). Law enforcement and regulators face an overwhelming problem not only to understand but appropriately combat these crimes that have eroded the financial security of countless Canadians and target the general public from all intersecting identity factors like gender, age, ethnicity, language, and socioeconomic status. According to the Canadian Anti-Fraud Centre, annual victim losses are escalating year over year into the hundreds of millions of dollars (Canadian Anti-Fraud Centre, 2023). This research study will strategically argue that pig butchering schemes represent a multibillion-dollar emergent hybrid threat to Canada's national security and economic prosperity and are emblematic of the commodification of foreign interference.