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BioEngineering

Click on the title for full description of SURE 2016 projects in BioEngineering.

BIO-001:  Printing nanodots on viscoelastic substrates for cell contractile work measurements
Professor: Allen Ehrlicher
E-mail: aje [dot] mcgill [at] gmail [dot] com
Telephone: 514-714-8239
Website 

Research Area: Cell mechanics and forces


Description:
Traction force microscopy is a well-established methodology to measure the local contractile forces exerted by a cell, and is accomplished by measuring the deformation of a soft elastic substrate by cell forces.  From this measured deformation, the strain is calculated, and by knowing the elastic modulus of the substrate, the forces are calculated. Key changes in physiology and pathology are reflected in these cell forces, such as in metastatic progression of cancer. In order to measure the substrate deformation, fiduciary fluorescent beads are typically dispersed randomly in the substrate; an image with the cellular contractile stress is compared to a references image with no cell stress, and the difference in bead positions allows the local stress to be calculated.  Here we propose to elimate the need for a stress-free image by printing a well-ordered array of fiduciary/adhesive fluorescent dots on the defomable substrate; by comparing the measured and expected positions, stresses and work can be calculated in real-time, allowing much simpler data analysis and acquisition. This project will create substrates with tunable frequency-dependent storage and loss moduli using polydimethylsiloxane (PDMS) silicone elastomers, and use microscopy to characterize active cell behavior on substrates with various mechanical properties.  We print the fiduciary markers using soft-lithography techniques onto the PDMS substrates, and measure their positions using confocal fluorescence microscopy.   Key skills: Familiarity fluorescence microscopy, cell culture, image analysis, and MatLab, are all highly useful for this project.

Tasks:
Stamping nanodot templates; culturing cells on substrates; using microscopy to image cells and dots; software and analysis to calculate forces

Deliverables:
A highly reproducible protocol for printing 200nm fluorescent cell-ligand dots on a deformable elastic substrate, and analysis code for determining dot displacement and the calculation of local stresses and work generated by cells.

Number of positions: 2
Academic Level: Year 3

BIO-002:  Dynamic functional motor connectivity in young and elderly subjects assessed from multimodal neuroimaging data
Professor: Georgios Mitsis
E-mail: georgios [dot] mitsis [at] mcgill [dot] ca
Telephone: 514-398-4344
Website

Research Area: Biosignal processing


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. In this context, the main objective of the present project is to use advanced signal and image processing methodologies for quantifying functional connectivity from multimodal neuroimaging measurements (simultaneous functional magnetic resonance imaging/electroencephalography-fMRI/EEG and magnetoencephalography - MEG), with an emphasis on time-varying (dynamic) connectivity, in order to investigate human motor connectivity in young and elderly subjects over multiple time scales. The experimental data will include both resting-state data, whereby the subjects do not perform an explicit task, as well as task-related data (hand grip), collected at McGill’s Brain Imaging Center. The aim is to identify connectivity-based measures related to motor performance and age-related motor decline. We will place particular emphasis on the timing events and patterns related to both motor task execution and resting-state connectivity, by exploiting the excellent time resolution of EEG, MEG and the excellent spatial resolution of fMRI. Further validation of the motor connectivity measures to be identified will yield a set of robust and sensitive biomarkers of age-related motor decline, which may ultimately guide personalized treatment strategies using exercise or stimulation protocols (e.g. transcranial direct current stimulation). The research team includes, besides Dr. Mitsis, an interdisciplinary team of McGill researchers, including neuroscientists/physiotherapists (Dr. Marie-Helene Boudrias) as well as physicists with an expertise in MEG (Dr. Sylvain Baillet) and MRI (Dr. Rick Hoge).

Tasks:
Student 1: Analysis of simultaneous fMRI-EEG data, extraction of functional connectivity measures and correlation to motor performance and age-related changes. Student 2: Analysis of MEG data, extraction of functional connectivity measures and correlation to motor performance and age-related changes.

Deliverables:
Student 1: Technical report summarizing the findings on fMRI-EEG based motor connectivity in young and elderly subjects Student 2: Technical report summarizing the findings on MEG based motor connectivity in young and elderly subjects

Number of positions: 2
Academic Level: Year 3

BIO-003: Rapid Prototyping of Biological Tissue Constructs
Professor: Joseph Kinsella
E-mail: joseph [dot] kinsella [at] mcgill [dot] ca
Telephone: 514-398-1899

Research Area: Tissue Engineering, 3D printing


Description:
Rapid prototyping, specifically 3D stereolithography and similar additive manufacturing methods, are enabling researchers to develop increasingly sophisticated biological templates for tissue constructs and devices that can contain cells or tissues. Since this equipment is relatively new to the field of Bioengineering there are several technological challenges that remain unaddressed. One of the leading challenges is that currently there are a limited number of materials that can be used with this technology that are suitable for Bioengineering applications (i.e., chemically inert, mechanically relevant, sterilizable, etc). This proposal will focus on developing novel biologically relevant photo-polymeric materials that can be patterned using commercially available 3D bioprinting tools. Upon development of the material, the polymer will be used to fabricate constructs that will enable either the growth of tissue or development of biologically powered microdevices.

Tasks:
The student will be tasked with developing 3D CAD files of printable objects, in addition to developing computational models (FEA) to predict the behavior of the construct/device in specific mechanical and/or electromagnetic environments. In addition, the student will participate in the development of the polymeric materials and physical evaluation. Finally, the student will use the construct, or device, as an in vitro test bed using cells or tissues.

Deliverables:
The student will be required to meet weekly with the PI to discuss progress and attend any group meetings held by the lab. The student will also prepare a written progress report to include a thoughtful and detailed analysis of the experiments and results to be due the week prior to the programs end, in addition to a detailed lab notebook. The student will also present a poster at the end of the SURE period.

Number of positions: 2
Academic Level: Year 3

BIO-004: Tracking and Treating Superficial Tumours with Radiopaque Radiosensitizing Nanoparticle Formulations
Professor: Joseph Kinsella
E-mail: joseph [dot] kinsella [at] mcgill [dot] ca
Telephone: 514-398-1899

Research Area: Nanotechnology


Description:
Each year in Canada more than 4,000 people are diagnosed with head and neck cancer, while worldwide head and neck cancer is the sixth most commonly diagnosed type of cancer. Of these patients, 1,150 died as a result of oral cancer in Canada in 2014. A majority of the Canadians diagnosed with this form of cancer undergo radiation therapy, which has been demonstrated as one of the most successful forms of treatment. While very effective in treating the tumour site the side effects of ionizing radiation can be painful and possibly mutilating, and can also be the cause of secondary cancers, so precise anatomical targeting of the radiation to the tumour tissue while sparing normal tissues is critical. However, this remains a challenge in radiation oncology, as malignant tumours do not have well-defined borders and are often surrounded by radiosensitive structures or cells. We hypothesize that using targeted X-ray Computed Tomography contrast probes targeted to the tumour cells, that are also radiosensitizing agents, will enable the development of image-guided external beam radiation therapies that can focus damage to the tumour site while minimizing off-target harm. In this work, we propose developing a new type of nanoparticle consisting of bismuth sulfide functionalized with a tumour penetrating peptide motif as the radiosensitizing compound. The bismuth sulfide particles, Bi2S3, are made of FDA-approved bismuth precursors and have many desirable photophysical properties including enhancing the effects of x-ray radiation therapy as the particles emit high energy Auger electrons and can generate radicals upon radiation exposure at the radiation energy levels currently used clinically. Developing an image-guided radiation therapy using radiopaque and radiosensitizing nanoparticles that can simultaneously provide enhanced X-ray image contrast and therapeutic capacity will limit the potential suffering that patients of oral cancer currently experience during treatment.

Tasks:
The student will work in a wet chemistry lab preparing, characterizing, and purifying nanoparticle formulations. The nanoparticles will be tested for toxicity using cells and tissues.

Deliverables:
The student will be required to meet weekly with the PI to discuss progress and attend any group meetings held by the lab. The student will also prepare a written progress report to include a thoughtful and detailed analysis of the experiments and results to be due the week prior to the programs end, in addition to a detailed lab notebook. The student will also present a poster at the end of the SURE period.

Number of positions: 2
Academic Level: Year 3

BIO-005: Bioinspired materials mechanics
Professor: Allen Ehrlicher
E-mail: allen [dot] ehrlicher [at] mcgill [dot] ca
Telephone: 514-398-8239
Website

Research Area: Bioinspired materials


Description:
From an engineering perspective, biology has incomparably mastered manufacturing and materials science. One of our research lab’s interests is studying how biological materials achieve such rich mechanics, and applying those principles to make radically new biomimetic materials that have the same wide dynamics and active mechanics of biology. In particular, biological systems generate forces by doing work, allowing structures to change shape, move, and change their mechanical properties. As part of a a collaborative multi-PI endeavor, we are using polymers including silicones and hydrogels to fabricate soft composites, and a variety of actuation methods to introduce movement. There is significant freedom in exploring these goals provided that deliverables are met.

Tasks:
Students will be responsible for a broad variety of tasks, including literature research, formulating and mechanically testing composites, and working in a diverse researcher environment. Students should have the highest motivation in both creativity and lab-work commitment.

Deliverables:
Students are expected to deliver a novel biomimetic material actuated in movement, moduli, or shape change by a method such as external EM fields, osmotic pressure, or light. This research must be meticulously carried out and documented in a report designed to be a methodology manuscript, and each student must present his/her research in frequent updates and in a final presentation in our group and poster in the SURE program.

Number of positions: 2
Academic Level: Year 3

BIO-006: Classification of Biological Nano-Objects According to Their Spatial Properties
Professor: Dan Nicolau
E-mail: dan_nicolau [at] yahoo [dot] com
Telephone: 514-398-7138

Research Area: Bio-Engineering


Description:
The spatial recognition of objects, from airplanes to human faces, is of ever-increasing interest in the present interconnected and crowded world. While this problem is tackled by humans by a myriad of image analysis and recognition algorithms implemented in dedicated software, a similar problem is seamlessly solved in Nature by the ‘image recognition’ between biomolecules – the cornerstone of all biological processes. However, and despite their theoretical similarity, presently only separate, specialised programs are used for image recognition for the macro-world, e.g., biometrics, and nano-world, e.g., drug discovery. The project will involve the use of existing in-house developed software for building images of biomolecules, followed by the development of an interface between structural databases, image building for the bio-objects present in these databases, and the archiving, classification and access to a database of molecular images. Additional information: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058896

Tasks:
Upgrade of the existing simulation procedure for molecular surfaces; running simulation for a small set of proteins; search for commonality of characteristics between the mapped molecular surfaces.

Deliverables:
Update the existing Biomolecular Adsorption Database (BAD); report regarding the property distribution on molecular surface. One conference paper is expected at the end of the project.

Number of positions: 1
Academic Level: Year 2, Year 3

BIO-007: Biocomputation with ‘Smart’ Biological Agents
Professor: Dan Nicolau
E-mail: dan_nicolau [at] yahoo [dot] com
Telephone: 514-398-7138

Research Area: Bio-Engineering


Description:
Many mathematical and real-life problems cannot, or are very difficult to be solved by the present computers which process the information sequentially and with extreme precision. Among these problems one can mention travel and production scheduling, class time tables, and cryptography. Despite this difficulty, these problems are solved easily by individual biological agents, from microorganisms to humans, who do not process the information sequentially, but in parallel, and who trade precision for heuristic decision making. Alternatively, some mathematical and real-life problems that cannot be solved by the present computers are also difficult to solve by individuals, due to the limited capacity of an individual to process the information in parallel, but can be solved heuristically by groups of individuals operating together either explicitly or tacitly. Among these problems one can mention behaviour of groups in panic situations, solving complex traffic problems, hierarchical self-organisation of groups in conflictual situations. To this end, the project aims to assess the individual and collective ‘computational power’ of individual biological agents in optimally partitioning the available space and taking optimal decisions. The possible applications range from medical to new algorithms and computer paradigms. The project involves either experiments, such as observing the ‘intelligent’ behaviour of microorganisms facing space confinement via their movement in microfabricated networks; or the modelling and simulation of their behaviour; or a combination of both. The ‘smart’ biological agent of choice is a fungus, which has been demonstrated as using intelligent algorithms for searching labyrinths. Additional information: http://www.youtube.com/user/BionanoinfoLiverpool?ob=0&feature=results_main

Tasks:
The project can be approached, depending on the student’s strengths, either from an experimental, or a simulation perspective. Experimental tasks comprise the fabrication of simple microfluidics structures; growth of microorganisms in microfluidics structures; observation and recording of microorganisms behavior. Simulation tasks comprise the translation of microorganisms behavior in logic rules and simple algorithms; and the simulation of microorganisms behavior in complex structures.

Deliverables:
Update the existing database of microorganisms behavior in confined spaces; or alternatively prepare a report on the optimality of microorganisms behavior. In both cases one conference paper is expected at the end of the project.

Number of positions: 2
Academic Level: Year 2, Year 3