韩国裸舞

It is well known that the transmission of respiratory viruses is strongly seasonal, but important knowledge gaps remain regarding what drives these dynamics. Emitted respiratory droplets are composed of biochemically complex respiratory tract lining fluids, which generally include mucin glycoproteins, the main polymer component of mucus. To infect a susceptible host, viruses must stay viable in these droplets, and an important aspect of this viability is the structure and integrity of their surface proteins involved in receptor binding. Here, we propose studying this using a system of virus-like particles (VLPs) which can be decorated with surface proteins specific to different respiratory viruses. The goal of the project is to expose VLPs to different climate conditions (i.e. temperature and relative humidity) in droplets of mucin gels, and visualize potential changes in surface protein structure using advanced imaging techniques.

Support graduate students in the production of VLPs and purification of mucins. Conduct experiments with the VLPs, including climate exposure and imaging. Analyze results using appropriate tools.

The cellular composition of the airways varies throughout the respiratory tract, as does the efficiency of mucociliary clearance (MCC), the process of replacement of the airway mucosal layer via the collective beating of cell cilia. These factors are strongly associated with pathogenesis and transmission of respiratory diseases, namely the observation of increased pathogenicity for viral infections of the lower respiratory tract and increased transmissibility for those of the upper respiratory tract. Additionally, the successful delivery of therapeutics to specific regions of the respiratory tract involves correctly accounting for lung architecture and mucosal biophysics. For instance, mucus barriers act as steric and biochemical filters that can exclude the passage of small molecules and delivery vehicles. Despite the importance of including mucosal barriers and lung architecture in models for viral infection and the design and delivery of therapeutics, dedicated experimental platforms for doing so are lacking. To develop such a platform, key preliminary experiments must be conducted to understand how the differentiation and function of cultured primary human bronchial epithelial cells can be manipulated in microfluidic environments to achieve variation in cell composition and MCC. This project focusses on the effect of channel / lumen size of the microfluidic conduits in particular.

The student will work with graduate students on the experiments, which will include developing microfluidic chips, culturing cells, and characterizing cell layers.

The yeast Saccharomyces cerevisiae has been used since ancient times in fermentation processes for the production of food and beverages. Following advances in genetic engineering, yeast has become a workhorse of modern biotechnology, preferred by industry due to its robustness and versatility. Despite recent advances (artemisinin, cannabinoids, opioids, etc.), the economic gain from these efforts has been limited. Efficient production of structurally complex chemicals requires the development of advanced biosynthetic systems. Extensive efforts have been made to understand and engineer yeast metabolism for the generation of efficient cell factories. However, less attention has been placed on studying yeast membrane properties and their contribution to biotechnological applications. Several cellular and molecular mechanisms are greatly related to membranes and could be limiting the performance of yeast cell factories. Such processes include general yeast fitness, the expression of functional membrane proteins, and the export of molecules or proteins. We hypothesize that differences in the properties between the membranes of yeast as host cell factories and other species as natural producers (e.g. plants) has a profound effect in the activity of heterologous membrane-bound enzymes and transport of substrates and products. We envision that by modifying the host membrane composition to mimic that of producer organisms or by engineering non-natural yeast membranes will improve performance of membrane-related bioprocesses reconstructed in yeast.

This project is available for iGEM students. Please contact Prof. Ignea (codruta.ignea [at] mcgill.ca) to apply for a position in this project.

Students will engineer lipid biosynthesis in yeast cells to modify the yeast membrane lipid composition and enhance lipid droplets formation. The resulting strains will be used for production of carnosic acid. Specific processes, including physiological parameters, heterologous pathways efficiency, formation of metabolic complexes and channeling of intermediate and final titers will be monitored. Carnosic acid production will be evaluated by GC-MS analysis.

The avian egg is a perfect incubator for the developing bird embryo, where all the nutrients are 鈥減re-packaged鈥� and are made bioavailable for assimilation in a timely manner. One macronutrient essential for the chick鈥檚 skeletal development is calcium, and it comes from the inner layer of the eggshell.

One challenge in studying calcium traffic pathways in a fertilized egg is the metastable nature of Ca complexes with other ions and proteins. Simply, when it comes into contact with water, it dissolves.
As part of this project, the intern will optimize anhydrous specimen preparation methods for X-ray microscopy and electron microscopy, will participate in imaging experiments, image processing and analysis.

Dissection of chicken embryos and embryonic membranes (a strong stomach is needed!). Work with fixatives and embedding media in a fume hood, polishing samples. Processing of 3D and 2D digital images in the Dragonfly software.

Imagine if you could explore rare historical artifacts, like ancient Egyptian mummies, up close, from anywhere in the world. What if you could examine them from all angles, from the outside and the inside, without risk of damaging these precious items? Our project aims to make this possible by creating a virtual reality (VR) museum. We are using X-ray-based 3D imaging technology to create digital 3D replicas of unique historic animal mummies from the Redpath Museum. Accurate processing of these replicas provides unprecedented level of detail, allowing us to highlight and explain specific features of each object, but are tedious to produce. The goal of this summer project is to prepare digital objects for a VR environment.

3D digital image processing, segmentation and annotation. Digital stitching and registration of multiscale images, animation.

Microbe fermentation has been used for production of primary and secondary metabolites with applications in a wide range of industrial sectors, such as health care, biofuels, biopolymers, and cosmetics. With recent advances in synthetic biology, fine chemicals, such as terpenoids, could be produced by Saccharomyces cerevisiae fermentation at industry scales, which is a promising alternative compared to plant extraction in an environmentally friendly way. The pESC vectors are a series of widely used episomal plasmids for expression and functional analysis of eukaryotic genes in S. cerevisiae, which allows to clone two gene fragments in opposite directions under the control of GAL1 and GAL10 inducible promoters. However, these vectors can not be used directly for chromosomal integration of genes into desired locus. Despite recent advances in genome editing capabilities for S. cerevisiae, the construction and chromosomal integration of large biochemical pathways for stable industrial production remains challenging. In this project, we will develop a simple dual use platform to assemble gene fragments for both plasmid construction and chromosomal integration based on homologous recombination. We will engineer efficient modules for CRISPR-based genome editing for multiplex engineering of target metabolic pathways in Saccharomyces cerevisiae. CRISPR modules of interest are CRISPR-associated endonuclease, intracellular availability of donor DNA, ssgRNA design, repair mechanism. Moreover, an efficient high-copy number CRISPR/Cas9-mediated genomic integration strategy will be engineered for stable protein expression of multistep biosynthetic pathways by localizing the donor DNA in the proximity of double strand breaks.

This project is available for iGEM students. Please contact Prof. Ignea (codruta.ignea [at] mcgill.ca) to apply for a position in this project.

The student's tasks consist of a balanced and comprehensive set of molecular biology and yeast genetic engineering techniques, including: mini-prep preparations, PCR, Plasmid construction (including restriction digests, ligations, and Gibson cloning). The final goal is to integrate a novel biosynthetic pathway in yeast for the production of target compounds. The student will design and construct plasmids with support and advice from graduate students.

Carotenoids are major constituents in plants, bacteria, and fungi that play roles in pigmentation, protection, and photosynthesis. They are precursors of Vitamin A, strong antioxidants, and protective agents against various conditions, such as inflammation, aging, cataracts, cancer, obesity, cardiovascular and neurodegenerative diseases. Owing to these biological activities, carotenoids are essential ingredients for human and animal health that must be ingested through food. This need has generated a growing commercial interest in carotenoid-based products as food supplements, nutraceuticals, colorants, cosmetics, and aquaculture and animal feed. To fulfill market demands, synthetic carotenoids are used in 80-90% of applications. These are chemically produced from raw petrochemicals and have shown reduced bioactivities and health issues. Consequently, synthetic carotenoids are not approved for human consumption and are mainly used for coloration purposes in aquaculture and animal feed sectors. Natural carotenoids are obtained by extraction from plants and algae or biologically produced in microbes by fermentation, and the associated procedures are more expensive than organic synthesis. We will develop a cost-effective strategy for production of natural carotenoids using baker's yeast, aiming to replace synthetic carotenoids in major applications. Yeast-made carotenoids will positively impact the Canadian and Quebec Agri-food sector at different levels: 1. Healthier aquaculture and animal feed products; 2. Cheaper and more available dietary supplements and nutraceuticals; 3. Microbial platforms for further production of carotenoids with unique bioactivities 4. Options for development of carotenoid-based probiotics.

This project is available for iGEM students. Please contact Prof. Ignea (codruta.ignea [at] mcgill.ca) to apply for a position in this project.

Students will perform a comprehensive set of multidisciplinary approaches including molecular biology, biochemistry, microbiology, and analytical chemistry. They will develop expertise in standard and Gibson cloning, media preparation, bacteria and yeast transformations, yeast cell culture, and liquid-liquid extraction. The student will generate a library of yeast strains dedicated to the production of different carotenoids and prepare a report on chassis evaluation.

The motor proteins kinesin and dynein move along microtubules to transport cargoes and organize microtubules in the cell. Our goal is to understand how multiple motor proteins operate in teams, and how they are regulated to perform complex functions like cell division and directed transport. Through extending single-molecule techniques to native organelles and living cells, we have developed advanced microscopy tools to measure the regulation, motility, and forces exerted by motor proteins with unprecedented resolution, and to manipulate the system by applying external forces to the cargoes through optical tweezers and controlling motor activity using optogenetics. We will image and manipulate ensembles of kinesin and dynein as they transport native cargoes in reconstituted systems and living cells to understand how kinesin and dynein motors interact, how they are controlled to direct intracellular trafficking, and how motor proteins are misregulated in neurodegenerative diseases including Alzheimer's Disease and Huntington's Disease.

• Student 1: Quantify the number and type of motor proteins associated with organelles using superresolution fluorescence microscopy.
• Student 2: Use the optogenetic inhibitors we developed to test the role of kinesin-1, -2, and -3 in the motility of endoplasmic reticulum-associated organelles.

Synthetic biology approaches have revolutionized the manipulation of bacterial cells for biotechnological applications. BioBricks have emerged as a powerful tool for standardized genetic engineering, and dedicated parts are currently available for various organisms. This proposal aims to develop and characterize an in-house comprehensive BioBrick toolbox for efficient bacterial manipulation. The following objectives will be pursued: 1. We will design and construct a series of novel BioBrick-compatible parts, including inducible promoters, ribosome binding sites, and antibiotic resistance markers to ensure modularity and ease of use. 2. We will develop novel bacterial expression systems to enhance DNA transformation efficiency, particularly for difficult-to-transform recombinant DNA part assembly reactions. Our toolbox will include integrative vectors for stable genomic incorporation and expression vectors for controlled protein production. 3. We will also create a suite of fluorescent reporters spanning the visible spectrum, optimized for codon usage in target bacterial species.

To address the challenge of genetic burden, we will systematically measure the impact of our BioBrick constructs on bacterial growth rates and other relevant physiological parameters. Using high-throughput screening methods and automated liquid handling equipment, we will identify parts that minimize metabolic load while maintaining functionality. We anticipate that this work will significantly advance the field of bacterial synthetic biology, enabling rapid prototyping and optimization of genetic circuits for applications in biotechnology, metabolic engineering, and fundamental research.

This project is available for iGEM students. Please contact Prof. Ignea (codruta.ignea [at] mcgill.ca) to apply for a position in this project.

In this project, the students will rationally design a set of integrative and expression vectors for specific bacterial strains. This strategy includes the design of:

• BioBrick parts
• A high-throughput screening method
• Genetic burden-free engineered bacteria
• Fluorescent reporters

The function of autonomic control centers in the brain is still incompletely understood, due to their location and small size. In this context, functional magnetic resonance imaging (fMRI) is currently viewed as the gold standard owing to its excellent spatial resolution. However, one of the main challenges when studying autonomic function with fMRI is that the BOLD fMRI signal is influenced both by neural activity caused by physiological fluctuations regulated by the autonomic nervous system (heart rate, respiration, blood pressure) as well as by these fluctuations directly (along with other factors such as motion). To address this, the use of multimodal neuroimaging combined with concurrently recorded physiological activity during tasks that elicit autonomic activations yields great promise. Importantly, it has become apparent that long COVID, which is affecting millions of Canadians, is associated with dysautonomia. To better understand these effects, we are currently collecting an extensive dataset (300 subjects) in a cohort of healthy and long-COVID individuals, which includes 7T fMRI, simultaneous EEG-fMRI and transcranial Doppler ultrasound during resting conditions and autonomic tasks (cold pressor, hypercapnia/hypoxia, slow breathing). In the present project, we will use these data to investigate autonomic activations in the healthy brain and compare them to those observed in long COVID. We will also examine the relation of these patterns to the underlying brain anatomy (venous and arterial density) as captured by structural MRI performed in the same subjects. The proposed work yields promise for identifying robust biomarkers for autonomic function and using them for therapeutic interventions.

Students will help organizing, preprocessing and analyzing the experimental data, using signal processing and neuroimaging data analysis methods. The aim will be to identify brain activation patterns in healthy and long COVID individuals and comparing them to each other.

Vibrio natriegens, a marine bacterium, has emerged as an alternative to the well-known fermentation workhorse, E. coli, showcased by a few research groups. The standout features of using V. natriegens fermentation system include a rapid doubling time of just 7 to 10 minutes under optimal conditions (at least twice faster than E. coli), making it one of the fastest-growing bacteria and enabling quicker bioproduction scaling. Additionally, its ribosome count exceeds that of E. coli, enhancing its protein synthesis capabilities and suitability for producing recombinant proteins. V. natriegens is also compatible with the E. coli compatible plasmid the pET expression system, facilitating quicker genetic engineering application scalability. Moreover, its non-pathogenic nature ensures safety in laboratories and industrial settings, and its metabolic versatility allows for the utilization of diverse substrates, providing flexibility in bioprocess design. Therefore, the potential for high-density cultivation using V. natriegens will lead to shorter production times and lower costs, highlighting the recently acquired importance of V. natriegens in synthetic biology and bioprocessing, as a superior alternative to traditional bacterial hosts. Considering these potentials, the following objectives will be pursued: 1. Engineering V. natriegens pDNA production for mRNA therapeutics; 2 Comparing the V. natriegens plasmid production to other strains of E. coli (BL21 DE2, Turbo). 3. Quality by design plasmid production comparison between V. natriegens and E. coli systems.

This project is available for iGEM students. Please contact Prof. Ignea (codruta.ignea [at] mcgill.ca) or Dr. Perumal (ayyappasamy.sudalaiyadumperumal [at] mcgill.ca) to apply for a position in this project.

Student will use several standard cloning and transformation techniques followed by plasmid isolation to engineer V. natriegens. PCR quantification and nanopore sequencing will be used to quantify the error rates and quality control aspects like the polyA tail of the plasmid. CRISPR-Cas9 and plasmid insertional cloning techniques will be employed to engineer V. natriegens for higher productivity. Plasmid engineering approaches will include ori modifications and fusion cloning techniques.

Minimal E. coli cells were previously engineered by genome recoding or reduction and have been proven to enhance the stability of lentiviral vector. Genome-reduction is specifically appealing for production purposes due to their expected fitness benefits, such as higher growth rate, higher biomass yield, improved genomic stability, and safer handling. This approach allows the removal of undesirable traits specific to pDNA plasmid production, such as insertion sequence (IS) transposition that may cause plasmid instability and low production. Moreover, the presence of mobile elements in plasmid DNA has raised regulatory concerns due to their potential to modify the biological characteristics and safety attributes of the vector DNA. We will identify and delete these genetic elements and in addition genes encoding transposases, phages, integrases, and recombinases, nonessential genes including K-islands, fimbriae, flagella, or genes involved in lypopolysaccharide biosynthesis and anaerobic respiration to minimize the E. coli and V. natriegensis genomes by ~25%. The engineered strains may show impaired growth under laboratory conditions. Thus, the best-performing strains will be subjected to adaptive laboratory evolution to facilitate self-optimizing unknown processes that may hinder strain-efficient performance. In addition, we will generate libraries of mutant cells by random engineering in the global transcription regulation machinery (gTME) to manipulate gene expression profiles in a transcriptome-wide manner. Selection of individual organisms exhibiting desired pDNA plasmid production, such as tolerance to different fermentation conditions, and the development of appropriate screening methods, will be targeted. Multiple omics measurements will be used to characterize novel bacterial strains and reveal the transcriptome and metabolome remodelling needed for growth recovery.

This project is available for iGEM students. Please contact Prof. Ignea (codruta.ignea [at] mcgill.ca) or Dr. Perumal (ayyappasamy.sudalaiyadumperumal [at] mcgill.ca) to apply for a position in this project.

The student will use several standard cloning and transformation techniques followed by plasmid isolation from bacteria. Engineering of bacterial strains will be performed by Cre-LoxP homologous recombination or CRISPR-based deletions using Cas9 mediated double-strand break coupled with non-homologous end joining repair.

In an aim to build a large-scale bioreactor-compatible selection of high-copy number strains of engineered novel microbial and minimal systems, this project will explore plasmid engineering strategies and importantly the use of microfluidics for screening the best-producing strains of different organisms developed in this study. We will establish V. natriegens as an alternative microbial platform to E. coli fermentation. In this project, apart from the physical parameters, genetic and plasmid optimization parameters will be extensively standardized. Tuning the plasmid copy number in V. natriegens has not yet been achieved, particularly as starting material for RNA biologics. The project will pursue a plasmid vector with a tunable origin of replication, such as pUC origin, which allows for copy number variation through changes in temperature or other physiochemical conditions. Screening of high-titre plasmid copy number strains will be pursued using engineering design-based microfluidics single-cell screening approaches. Droplet microfluidics-based confined environments with a variety of physical and nutritional conditions will be tested to explore the best plasmid titre yields in the selected bacterial strains. The use of microfluidics at the single-cell level provides the ability to screen rapidly in a short period of time and in real-time for the producer strains and enables scale-up strategies to be used in the screened strains. A microfluidic platform that can monitor the bacterial production titre continuously and for multiple generations using microfluidic devices similar to the mother cell will be used in this project.

This project is available for iGEM students. Please contact Prof. Ignea (codruta.ignea [at] mcgill.ca) or Dr. Perumal (ayyappasamy.sudalaiyadumperumal [at] mcgill.ca) to apply for a position in this project.

Students听will use CRISPR-Cas9 to knock out native restriction-modification systems that might degrade foreign DNA (pDNA), optimizing the host for plasmid stability and yield. High-throughput screening approaches will be pursued by microlithography approaches, specifically by using SU-8 fabrication techniques and PDMS replica-soft lithography approaches. The student will also use the extensive microscopy-based readout at single cell level.

The cell is the fundamental unit of life, yet the inner workings of the cell are far more complex than we ever imagined. Without a good model of the cell, it is difficult to develop new drugs to repair diseased cells, or build new cells to produce much-needed chemicals and materials. A key step towards building a working model of the cell is to map the complex network of interactions between thousands of tiny molecular machines in the cell called proteins. This project will focus on computer modeling of protein structures and networks. Various experimental and computational datasets on protein structures and networks will be integrated and visualized. The resulting integrated protein structures and networks will then be annotated with evolutionary and disease properties, with the aim to understand how protein structures and networks evolve, and how disruptions in protein structures and networks lead to disease.

• Literature review
• Becoming familiar with publicly-available datasets on protein structures and networks
• Becoming familiar with existing computational tools on modeling protein structures and networks
• Computer programming

Therapeutic hydrogels
have been designed as tissue engineering scaffolds and as
injectable drug delivery carriers for the sustained release of
regenerative compounds. Delivering hydrogels to precise locations
of an internal wound or surgical site remains an outstanding
challenge. This project will develop a hydrogel depositing robot
using a 3D continuum printing tool as an in situ 3D bioprinter.
This includes designing, building, and modeling a miniature
continuum printing tool tip capable of extruding tissue adhesive
gels and integrating the tool into a 6 Degree of Freedom (DoF)
robotic arm. The final objective is to develop the instrument for
automated image-guided printing by integrating the robotic system
with an imaging system. The short-term goal is to evaluate the
robotic printer via proof-of-concept experiments that demonstrate
regenerative gels precise and reproducible extrusion. Mid-term
goals include developing and modeling the gel flow, designing
extrusion systems and tool heads, and integrating the
image-guided cameras, image processing, and controls. This
project is co-advised by Profs. Audrey Sedal and Matt Kinsella.

The ideal student for this role has well-demonstrated enthusiasm
for research, excellent mechanical design skills as evidenced in
a design portfolio, and an interest in surgical robotics. You
will:
1. Research patents, publications, textbooks, and software
related to the design, build, and testing of medical robotics and
continuum printing tools.
2. Design and build several prototypes of mm-scale continuum 3D
printing tools and attachments to a 6DoF robotic arm.
3. Use robotics programming tools to integrate the control of the
printing tool with the robot arm鈥檚 motion.
4. Perform proof-of-concept demonstration of hydrogel extrusion.
5. Analyze kinematics, printing parameters and their outcomes,
and data generated during the build and proof-of-concept
experiments.
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Machine learning and deep learning models are being
integrated into biosensing projects for their data processing and analysis capabilities. Mahshid labs develops translational bio-nano-medical devices for point-of-care diagnostics and therapeutics applications. The lab is conducting translational research in nanomaterials-based sensing, point-of-care microfluidic devices, and integration approaches. We combined
nanostructured platforms with optical readouts like bright field microscopes and surface-enhanced Raman spectroscopy (SERS) to generate various libraries. We have available image libraries from colorimetric assays for the detection of pathogens like bacteria and viruses, and spectral libraries derived from glioblastoma multiforme and medulloblastoma cancers.
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