Program: Health Research BC - Mitacs Industry-Based Opportunity

Safety Assessment of Antimicrobial Peptides

Antimicrobials kill or halt harmful microbes. The most common class, antibiotics, once turned lethal infections into routine cases, but only a few new antibiotics have appeared since 1987. Meanwhile, bacteria keep evolving, making many existing drugs unreliable. Without new and practical options, deaths from resistant infections are projected to climb steeply in the coming decades.  A promising alternative is antimicrobial peptides (AMPs), which are short protein molecules that can create holes in bacterial cells, block vital processes, or boost our immune response. Machine-learning tools have already predicted hundreds of potent AMPs. However, assessing how quickly bacteria might learn to resist them remains challenging.

 

To meet this need, we will build an automated, high-throughput resistance test (“iAMR”) that lets a liquid-handling robot challenge bacteria with low, repeated doses of 28 new AMP-bacterium pairs over 21 days while measuring growth every 30 minutes. Samples from each time-point are frozen for future DNA and RNA sequencing to reveal exactly how resistance, if any, appears.

 

Results will be used directly in Amphoraxe’s AMP development pipeline, help regulators judge long-term efficacy, and provide an open-source protocol that other labs can adopt. In short, the project aims to fast-track safer peptide antibiotics and keep Canada ahead in the fight against antimicrobial resistance.

 

Keywords: antimicrobial resistance, antimicrobial peptides, automated liquid handling, high-throughput screening, iAMR

The proposed novel passive hand tremor attenuator for Parkinson’s patients

This research project, funded through the Health Research BC and Mitacs Industry-Based Program, focuses on developing a wearable device to help people living with Parkinson’s disease and other movement disorders manage hand tremors. The work is led by Dr. Hadi Mohammadi and carried out by postdoctoral intern Dr. Dylan Goode in collaboration with Summit Innovation Ltd. and the University of British Columbia Okanagan.

 

Tremors are a common and often frustrating symptom of Parkinson’s disease and essential tremor. They can make everyday tasks like eating, writing, or getting dressed very challenging. Although treatments such as medication and surgery are available, they are not always effective, especially for hand tremors.

 

This project is creating a small, lightweight, and fully passive device that reduces tremors using smart mechanical design. The device absorbs the small, rapid movements that cause tremors without affecting a person’s normal voluntary motions. It is being designed to be safe, comfortable, and easy to use in daily life.

 

The device is being refined through computer simulations and real-world testing, including with older adults in long-term care facilities in Kelowna. The goal is to offer a practical and affordable solution that improves quality of life and independence for people living with tremors.

 

Keywords: Parkinson’s disease, essential tremor, wearable medical device, hand tremor, passive actuator, biomedical engineering

Shaking in the Wings: Creating a Drama-based Curriculum Derived from Actor Education to Address Music Performance Anxiety

The project goal is to investigate how curriculum derived from actor education can be effective as an educational intervention on how in educating musicians to mitigate music performance anxiety without the use of pharmaceutical and psychological interventions. This project consists of original research in a sub-field of music performance anxiety that is virtually non-existent (i.e., adapting acting education) and has the potential to solve a systemic issue that has a significant and negative impact on the health, wellbeing, and performance of most professional musicians.

 

To understand the nature of this work, it is important to discuss music performance anxiety and the negative impacts it has on musicians. Performance anxiety is a subcategory of social anxiety. Music performance anxiety occurs when a performing musician experiences cognitive impairment, and disruptions to behaviour, motor control and/or physiological symptoms. These debilitating impacts interfere with the performer’s body, breathing, control of instrument, and causes stress including shaking, fainting, and nausea. Music performance anxiety often leads to career abandonment and the reliance on pharmaceuticals. In a survey, 98% of 447 professional musicians reported experiences of music performance anxiety (Beder, 2017). In the researcher’s past survey work, she has found little evidence of curriculum in British Columbia on how to manage music performance anxiety. Also, many studies focus on pharmaceutical and psychological intervention methods for students and musicians, rather than curriculum, and these methods require specialist knowledge to facilitate, beyond the scope for most post-secondary teachers. This research project has a practical solution to this systemic issue: educational interventions using acting education. Acting, as a therapeutic technique, an art form, and an experience, can be transformative—it is a powerful technique that changes the performer into a character and changes the story into an inspiring narrative free of anxiety.

 

Beder, J. (2017). The 2015 musicians’ health survey results. Senza Sordino, 55(2). International Conference of Symphony and Opera Musicians. https://www.icsom.org/senzasordino/2017/06/ the-2015-musicians-health-survey-results/

 

Key Words: wellness education; music performance anxiety; Canadian curriculum

LNP-mRNA as a treatment for neurological dysfunction of Gaucher Disease

Severe brain disorders are the second leading cause of death and leading cause of disability worldwide. Drug development for these disorders has remained a significant challenge due to the protective blood brain barrier that shields the brain from the rest of the body – including therapeutics. This collaborative research project between the MacVicar Lab (UBC) and CereCura Nanotherapeutics is focused on a solution to this longstanding problem, using a novel technology that empowers the brain to manufacture its own medicines inside the brain compartment. This approach builds upon the lipid nanoparticle (LNP) and messenger RNA (mRNA) technologies that were used in the COVID vaccines to enable long-term, stable production of protein-based therapeutics to treat brain disease. Dr. Andrews’ project is to engineer next-generation mRNA therapeutics using human-derived stem cell ‘neurosphere’ culture systems to screen for sequences with optimal protein production, durability, and causing minimal inflammation. His work aims to generate a suite of LNP-mRNA candidate therapies to produce the vital enzyme GBA1 in the brain, which is a key target in the rare disorder neuronopathic Gaucher Disease, but also Parkinson’s Disease. This work will lay the crucial foundation for LNP-mRNA as a new drug class to treat patients with untreated brain disorders.

 

Dr. Daniel Andrews is a postdoctoral research fellow in the MacVicar Lab at the University of British Columbia Djavad Mowafaghian Centre for Brain Health. His internship is jointly funded by Michael Smith Health Research BC, Mitacs, and CereCura Nanotherapeutics, through the “Health Research BC-Mitacs Industry-Based Opportunity” partnered funding program.

 

Keywords: lipid nanoparticle (LNP), messenger RNA (mRNA), therapeutics, platform technology, brain disorders, neurodegeneration, Gaucher Disease, Parkinson’s Disease

Development and validation of in vivo models of acute bacterial infections for use in novel drug development

Bacterial infections are one of the main causes of mortality and long-term patient complications worldwide. For example, pneumonia is the number one cause of death in children under 5. The primary driver of toxicity resulting in organ failure and death during these infections are components of the bacteria themselves, called endotoxins. These are components of the bacterial membrane that the body’s immune system senses and then triggers massive inflammation as a result, and this causes associated organ damage. When present in high abundance, this can cause severe inflammation resulting in death. The condition in which an infection results in high levels of endotoxin in the blood is referred to as endotoxemia and is the main driver of mortality in these infections. Endotoxemia conditions include pneumonia, and others for which few good therapeutics exist. Developing drugs to reduce the time to resolution of endotoxemia is the goal of this proposal.

 

Over decades it has been established that endotoxins are sequestered and cleared from circulation via high- and low-density lipoproteins (HDL and LDL respectively). These complexes bind endotoxin and are then cleared into the bile via the liver in a pathway overlapping that of cholesterol metabolism. From extensive clinical studies, it was recently discovered that patients with mutations in genes that result in increased function in the HDL and/or LDL pathways have superior outcomes from severe endotoxemia-related infections such as sepsis than the average population. For example, patients with mutations in the PCSK9 gene have a ~85% overall survival rate after 1 year, whereas this is ~60% in the average population. This and other proteins are largely made in the liver, which is a highly druggable organ using genetic drugs delivered via lipid nanoparticles (LNP).

 

Resolve Nanotherapeutics is a preclinical drug development company creating LNP RNA drugs that will either mimic or improve on these clinical observations by upregulating endotoxin clearance pathways after intravenous infusions. RNTx has significant expertise in RNA LNP drug development but critically lacks disease challenge models to test its drugs – a non-trivial task that will dictate the direction of clinical development of any new drug formulations. We have identified a strong bacterial infectious disease post-doctoral fellow interesting in developing and testing of drugs in at least 3 in vivo challenge models, and setting these up and doing efficacy testing is the basis of this proposal.

 

The aims are as follows:
1. Develop an in vivo model of bacterial pneumonia for at least 4 diverse bacterial pathogens
2. Develop and in vivo model of bacterial sepsis
3. Develop an in vivo model of chemotherapy induced (febrile) neutropenia

 

The fellow will develop hands on skills for in in vivo infection models and testing drug formulations therein. They will also gain experience in drug development, both by exposure to the drug development process in terms of design, but critically learn to assess in vivo requirements such as pharmacokinetics, biodistribution, toxicity, efficacy, and many other evaluations. These are invaluable skills highly translatable to other sectors of drug development.

The project will greatly accelerate the capacity of Resolve NTx to perform drug candidate efficacy testing and ultimately chart the fastest path to clinical to get these potentially critical drugs into patients as fast as possible.

Privacy-Preserving Human Activity Recognition for Healthcare using Large Vision-Language Models

Background

The world is aging quickly. Most senior or elderly people prefer to aging at homes. Many of them live alone, but they face many challenges to their health and safety. On the other hand, in the value-based healthcare system, there are growing demands to monitor the activities of patients at homes, and even identify some diseases earlier to reduce the cost to the healthcare system. How to monitor the health and safety of seniors and patients while respecting their privacy is a great challenge.

 

Since 2018, AltumView has developed the Sentinare smart activity sensor for senior care and remote patient monitoring. It uses the latest AI technology to monitor the activity of people, collect health statistics, and notify caregivers when emergencies such as falls are detected. To protect privacy, only stick figure animations are transmitted instead of videos.

 

AltumView has become a global leader in privacy-preserving AI for healthcare. Its product received CES 2021 Innovation Award Honoree, and is one of only three fall detection devices integrated into Amazon’s Alexa Together emergency service.

 

The aims/ objectives of the project

Currently AltumView’s algorithms are operating in the sensor. Due to the limited computational resources in the sensor, these algorithms can only detect basic actions such as standing, sitting, and falling.

 

In this project, we aim to develop cloud-based algorithms to recognize more complicated activities, including activities of daily living (ADLs), such as eating, drinking, and cooking. Being able to recognize these activities will provide valuable information to the family and doctors to monitor the health and safety of the seniors and patients.

 

Based on the stick figure data from AltumView’s product, our long-term goal is to develop algorithms to perform cognitive assessment, and identify some behavioral diseases earlier, such as Parkinson’s disease, dementia, anxiety, depression, and autism, by collaborating with more physicians and hospitals.

 

The skills/ competencies the intern is expected to develop through the internship

The intern should have good knowledge of deep learning. In the project, the intern will learn more on privacy-preserving AI, especially the latest large-model-based AIs. The intern will also learn valuable product development experience, and how to combine research and product development under various constraints.

 

How the project and internship will support the company

In this project, the intern will learn and develop algorithms using various latest tools in AI, such as Graph Convolution Network (GCN), Graph Transformer (GT), and large-language-models (LLM) and large-vision-language-models (VLM) such as ChatGPT and Sora, which have demonstrated revolutionary performances in many fields. AltumView is also the only company in the world that has accumulated millions of hours of privacy-preserving stick figure data, which is extremely valuable in developing large-model-based AI algorithms.

 

The intern will focus on two aspects:

  1. We will focus on developing stick-figure-based methods, since AltumView sensor only transmits stick figures to the server. Although there have been some stick figure-based GCN and GT methods, stick-figure-based VLM methods have not been well studied. This creates a good opportunity to make some breakthrough in this unique and important field, given the enormous practical application potential of AltumView’s product. It will significantly enhance AltumView’s competitiveness in the market.
  2. We will focus on developing low-cost and high-performance algorithms. Since our algorithms only use stick figure instead of videos, its complexity is already much lower than video-based methods. If we can further reduce the complexity of stick-figure-based methods without sacrificing too much the performance, we will have a great advantage compared to other products.

 

In summary, this project will develop novel privacy-preserving AI algorithms for healthcare, apply them to AltumView’s product, enhance its leadership in the market, help more seniors and patients around the world, and contribute to Canada’s economy.

Developing Xeno-Free Media for Scalable Production of Dermal Sheath Cells

This project focuses on developing a serum-free, xeno-free culture medium for the scalable production of dermal sheath cells (DSCs) for use in regenerative medicine and cell therapy. DSCs are specialized cells found in hair follicles that have significant potential for applications such as wound healing, skin repair, and tissue engineering. However, current methods for growing these cells rely on animal-derived serum, which can lead to variability, safety concerns, and regulatory challenges for clinical use.

 

By creating a serum-free medium, this research aims to enable safer, more consistent, and ethically sound production of DSCs for therapeutic purposes. The project combines biomaterials engineering and cell biology approaches to optimize cell growth, viability, and function in this new medium. The long-term goal is to support the development of advanced cell therapies that are ready for clinical translation.

 

This research is supported through match funding provided by Mitacs and Health Research BC. It contributes to advancing cell-based therapies and strengthening British Columbia’s biomanufacturing and biotechnology capacity.

 

Keywords: dermal sheath cells, serum-free media, xeno-free culture, cell therapy, regenerative medicine, tissue engineering

Changing Patterns of Retirement in Northern BC – Implications for Health Policy and Planning

Forecasting plays a critical role in decision-making systems, particularly in healthcare systems modeling. Comprehending the dynamics of healthcare systems is essential for effective planning to meet future needs. In British Columbia, the population is projected to continue growing and aging, trends that are expected to lead to increased demand for healthcare services. Northern British Columbia in not an exception. This research aims to develop a comprehensive dynamic model to project healthcare demand in Northern British Columbia (BC). A particular focus would be on the effects of intra-provincial migration patterns, specifically the movement of retirees from Southern BC to Northern BC. A computer-based model will be created to help understand and predict how different parts of the healthcare system work together over time. The developed model is grounded in a systems thinking approach, allowing us to represent and understand complex systems by showing how different parts influence each other over time through feedback loops. With the collaboration of Northern Health, this research will discover key factors, such as aging and migration, that influence the demand for healthcare services, considering the available supply of resources. By utilizing the constructed method, the research will simulate the complexities inherent in healthcare demand forecasting and will identify strategies for effective resource allocation and policy planning. Moreover, it will provide valuable insights for improving healthcare delivery in Northern BC.

 

Keywords: Northern British Columbia; Intra-provincial Migration; Dynamic Healthcare System; Simulation

Innovating Water Purification: Electrophotocatalytic Technologies for PFAS Removal

This research project is supported through the 2024 Mitacs and Health Research BC funding competition, with contributions from Mitacs and Health Research BC.

 

Per- and polyfluoroalkyl substances (PFAS) are a group of man-made chemicals used in products like non-stick cookware, firefighting foam, and water-repellent fabrics. Unfortunately, PFAS are highly persistent in the environment and have been linked to serious health concerns. Because they don’t break down easily, they often contaminate water and soil, posing long-term risks to ecosystems and public health.

 

Our project focuses on developing and improving a new, energy-efficient technology that can break down PFAS safely and effectively. Using a special material called titanium dioxide in the form of nanotube arrays, the system applies a low electric current to destroy PFAS and convert them into harmless substances like carbon dioxide and fluoride.

 

We are now working to understand how this system can be scaled up for use in real-world settings like wastewater treatment plants and polluted soil sites. This includes testing how well it performs under different conditions and how long the materials can last before needing replacement.

 

By helping to develop a sustainable solution to PFAS pollution, this project supports environmental restoration and public health protection in Canada and beyond.

 

Keywords: PFAS, environmental remediation, water treatment, sustainable technology, public health, Health Research BC, Mitacs

The effects of isocapnic respiratory muscle endurance training on the multidimensional components and neurophysiological mechanisms of exertional breathlessness in healthy adults

This research being done into the effectiveness of targeted respiratory training with subjects identified with unsatisfied inspiration will have great benefit to the company as it expands its user base, and increases awareness of the effectiveness of their product and training methodologies. Olivia (intern) will gain new skills by working with an industry partner to better understand how her current research skills can inform the development of effective medical devices. Additionally, this work will complement her previous research in exercise and breathlessness, providing hands-on experience in testing the efficacy of a medical device on breathlessness and respiratory physiology. Lastly, gaining experience working in industry will be an invaluable asset as she moves forward in her research career.