黑料不打烊

Description

Optical tweezers (or optical traps) use a tightly-focused laser beam to exert forces on micron-sized refractive objects. By attaching motor proteins to small latex beads, we can measure the forces exerted by single molecules. Our lab has also developed techniques to measure the forces exerted by motor proteins and characterize the viscoelastic environment in living cells. Here, we will modify our current optical trapping systems to add two important capabilities. First, we will develop a force-feedback optical trap that allows us to exert constant forces on motor proteins as they move along cytoskeletal filaments. The force is measured by collecting the light that passes through the bead onto a quadrant photodiode, and the the position of the trap is controlled through an acousto-optic deflector. Second, we will develop the ability to simultaneously manipulate several beads by rapidly switching the position of the optical trap such that multiple time-shared optical traps are formed. Multiple traps will be used to measure the mechanical response of the cell over several length-scales.

Tasks per student

Student 1: (1) Develop optical tweezers capable of manipulating single molecules and measuring their nanometer-sized displacements and pN-level forces. (2) Program a simple feedback controller to maintain constant forces. Student 2: (1) Develop software to control the acousto-optic deflector to form multiple, time-shared optical traps. (2) Use the optical tweezers to examine the viscoelastic properties of the cellular environment.

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Number of positions

2

Academic Level

No preference

Description

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 cell division, and how motor proteins are misregulated in neurodegenerative disease and cancer.

Tasks per student

Student 1: Express and purify proteins and organelles. Perform single-molecule in vitro motility assays. Analyze images. Student 2: Develop micro patterned microtubule arrays to reconstitute spindle assembly in vitro.

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Number of positions

2

Academic Level

No preference

Description

The development of artificial organs represents a promising way to shorten transplant waitlists and devise innovative cell therapies. Among others, artificial pancreas, liver, cardiac, and kidney tissues are currently being developed around the world. A key component in translating this technology to a clinical setting involves proper mass transport throughout these thick constructs. Physiologically, nutrients, waste, and biomolecules are transported to and from organs through blood vessels. As such, artificial vascularization has become a prevalent topic in the fields of Tissue Engineering and Regenerative Medicine. Replicating native tissues and blood vessels can be challenging due to the detailed microstructure and the complex organization of cells and materials within human physiology. A way to accomplish this is through modular bioprinting (3D printing of live cells). Through a multi-nozzle approach, the resolution associated with additive manufacturing can enable spatial localization of different cell types and biomaterials. The goal of this work is to engineer a platform where artificially vascularized tissues can be fabricated, tested, cultured, and studied in vitro. This work will involve the use 3D printing to fabricate artificial tissues and custom parts for the tissue testing platform. Specifically, through an understanding of computer-aided design (CAD), aseptic technique, fluid dynamics, cell culture, vascularization, and manufacturing, this project is expected to lead to the conception of a laboratory-scale perfusion platform suitable for the in vitro culture of artificial tissues. Note: please e-mail corinne.hoesli [at] mcgill.ca directly with a cover letter, CV, and transcript before submitting your SURE form.

Tasks per student

Computer-assisted design (CAD); 3D printing; cell culture of beta cell lines; aseptic technique; rheology; computer simulation/modelling; literature review; design of experiments; data analysis; oral and written presentation of results; presentation of research progress; contribution to lab duties.

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Number of positions

1

Academic Level

No preference

Description

About 12% of worldwide mortality directly linked to coronary artery disease, characterized by narrowing of the arteries nourishing the heart. This necessitates the implantation of a vascular stent, a cylindrical mesh that is implanted in the narrowed area to allow maximum blood flow. Due to biocompatibility issues, the stented artery can re-narrow, putting the patient at risk of heart attack and myocardial infarction. Endothelial cells create the most biocompatible blood contacting surface known to man. Health endothelial cells can also regulate the overall health and function of vascular tissue. Modifying the surface of stents with specific biomolecules can potentially enhance the endothelial coverage of the stent. The biomolecules would target the recruitment of endothelial progenitor cells (EPCs) to the surface, protecting against stent failure and causing regeneration of the arterial tissue. The objective of this project is to modify the surface of common stent materials to introduce the required biomolecules. Specifically, the goal of the internship project is to study the efficacy and longevity of the surface functionalization strategy. The results of this work could play a key role in designing a new generation of surface modified vascular scaffolds to improve the quality of life and life expectancy in people with heart disease. Note: Effective communication in French is desirable for collaboration with the team at Universit茅 Laval, including potential visits to the laboratory of Ga茅tan Laroche in Qu茅bec city. Please e-mail corinne.hoesli [at] mcgill.ca directly (cover letter, CV, transcript) before submitting your SURE form.

Tasks per student

Surface characterization; Modify biomaterial surfaces using wet chemistry; human cell culture; fluorescence microscopy; image analysis, experimental design; data analysis; data presentation at group meetings; collaboration with research groups in chemical engineering and medicine at 黑料不打烊, Universit茅 Laval, and the Montreal Heart Institute.

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Number of positions

1

Academic Level

No preference

Description

Vascularization of medical devices and engineered tissues is necessary for nutrient transport and waste removal as well as to ensure successful graft integration with host tissues. The cells that line the interior of blood vessels are endothelial cells (EC) and they originate from endothelial progenitor cells (EPC). EPCs are involved in angiogenesis and wound repair by recruitment to sites of repair, proliferation, and differentiation to mature ECs. Studying the conditions which optimize this process would be of great interest to advance endothelialisation strategies. One major challenge here is that distinguishing between EPCs and ECs is difficult and requires time-consuming end-point analyses. A reporter EPC line that expresses a fluorescent protein upon differentiation into EC would allow for rapid tracking of the process in real-time. One step in developing this reporter line is establishing the source of the EPC and validating the cell line. EPCs derived from human pluripotent stem cells (hPSC) provides the advantage of having a theoretically unlimited supply of cells and more homogeneity in the population. The objective of this project is to optimize the culture conditions leading to EPC production from hPSCs using statistical design of experiments (DOE). The DOE approach will include the concentration of factors added during culture and the timing/duration of their addition for different hPSC lines. This research will be essential for the development of the reporter EPC line that in turn has the potential to advance tissue engineering endeavours. Note: please e-mail corinne.hoesli [at] mcgill.ca directly (cover letter, CV, transcript) before submitting your SURE form.

Tasks per student

The trainee will be involved in experiment design (statistical DOE and modelling of response surfaces), data acquisition, and data analysis. Wet lab techniques could include mammalian cell culture, fluorescence microscopy, flow cytometry, qPCR, Western blotting, immunocytochemistry, molecular cloning, and more. The trainee will also be expected to present updates at group meetings

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Number of positions

1

Academic Level

No preference

Description

High cell purity and the need for a large number of cells are two critical roles for cell therapy and regenerative medicine applications. Due to their larger surface area compared to flat substrates, microcarriers are commonly used to expand anchorage-dependent cell types in suspension cultures. However, microcarriers are most commonly used for cell lines and their potential for the expansion of primary human cells with high proliferative potential has not yet been fully investigated. The objective of this project is to design microcarriers tailored for the expansion of human endothelial progenitor cells which have significant potential for the treatment of heart disease. Specifically, endothelial colony-forming cells (ECFCs) will be isolated from peripheral blood, and then grown on custom microcarriers developed in our laboratory. The adhesion and growth kinetics on these customized microcarriers will be characterized and compared to standard microcarriers available commercially. The long-term goal of this project is to develop the next generation of 鈥渟mart鈥� microcarriers for applications in cellular therapy to treat a wide range of degenerative disease including heart disease. Note: please e-mail corinne.hoesli [at] mcgill.ca directly (cover letter, CV, transcript) before submitting your SURE form.

Tasks per student

Preparation of standard operating procedure and experimental design, data analysis, running statistical models, cell culture, immunohistochemistry, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA) and flow cytometry.

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Number of positions

1

Academic Level

No preference

Description

The exceptional capacity of the brain to process complex stimuli arises largely from the presence of intricate interactions between different regions. Therefore, understanding connectivity holds one of the major keys for understanding brain function in health and disease. More recently, there has been much interest in dynamic functional connectivity, i.e. how connectivity patterns vary over time. In this context, the main objective of the present project is to use advanced signal and image processing to better understand the nature of dynamic functional connectivity. Specifically, we will use collect/analyze multimodal neuroimaging data (simultaneous EEG-fMRI, Doppler ultrasound and fNIRS) during resting-state conditions, as well as during a variety of physiological and sensory tasks (CO2 inhalation, breath holds, eyes open/closed, visual/auditory stimuli). We will specifically investigate the possible source of time-varying functional connectivity patterns, such as physiological factors (i.e. fluctuations in physiological signals such as heart rate, respiration and arterial CO2) and electrophysiological signatures, such as power in different frequency band of the EEG signal. To achieve this we will use nonstationary signal processing methods such as wavelets and time-varying multivariate autoregressive models that our lab has developed. Multimodal imaging methods are very promising to better elucidate the exploiting the excellent time resolution of EEG, MEG and the excellent spatial resolution of fMRI. They also yield promise for identifying more robust biomarkers for earlier/more accurate diagnosis of brain disorders as well as targets for therapeutic interventions (e.g. noninvasive brain stimulation).

Tasks per student

The student will help in the collection of experimental data at 黑料不打烊鈥檚 Brain Imaging Center (BIC), as well as analyze the experimental data. The aim will be to better understand how signals recorded with different modalities may be used to quantify dynamic connectivity patterns, e.g. how does EEG signal power in different frequency bands affect the slow fluctuations observed with the fMRI BOLD signal?

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Number of positions

1

Academic Level

Year 3

Description

Syncope describes a transient loss of consciousness resulting from cerebral hypoperfusion, with rapid and spontaneous recovery after which consciousness is regained. It is a common clinical problem that affects up to 3.5% of the general population. The clinical approach to evaluation of syncope primarily involves careful history with physical examination occasionally corroborating abnormalities suspected (orthostatic hypotension or structural heart disease as examples). In many instances however, the patient arrives for evaluation and appears well. As a result, in close to 40% of cases, the exact cause of syncope remains elusive, and 30% of affected patients experience recurrent episodes. Moreover, there are no predictive strategies that are available that may provide patients warning of impending events. 韦he main aim of the present project is to identify robust quantitative markers of VVS from physiological signals recorded in VVS patients during presyncope, using shorter term (minutes) physiological data recorded in the lab (head-up tilt; HUT) as well as longer term (days/weeks) data recorded during everyday life using wearable devices. We will use advanced signal processing, systems modeling and machine learning methods to obtain insights into underlying mechanisms specific to clinically identifiable patterns of VVS and to obtain predictive markers of impending VVS. We will also use patients with orthostatic hypotension as a validation population to validate the wearable technology and identify its limits. The specific objectives are: (i) Using already available data from VVS patients with HUT-induced syncope, we will identify VVS-related markers by examining waveform characteristics of individual signals, tracking their time-varying properties. (ii) We will identify additional markers by quantifying dynamic interactions between signals and using time-varying mathematical models to elucidate individualized physiological mechanisms of VVS. (iii) Using machine learning methods, we will select the most informative markers and validate their specificity against patients with VVS who did not exhibit HUT-induced syncope, as well as OH patients. (iv) To further validate these markers and make the transition to wearable device data, we will analyze physiological signals recorded using wearable devices during standard HUT testing in the lab in VVS and OH patients as well as during everyday life.

Tasks per student

The student will analyze experimental data collected at the Jewish General Hospital and during everyday life. The aim will be to identify markers of impending seizures using heart rate and blood pressure waveforms and mean value time series.

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Number of positions

1

Academic Level

Year 3

Description

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.

Tasks per student

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

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Number of positions

3

Academic Level

Year 3