Dr. Ned Budisa
Canada Research Chair in Chemical Synthetic Biology, University of Manitoba
Dr. Hans-Joachim Wieden
Lead for BioSciences Entrepreneurship and Industry Partnerships, Faculty of Science, University of Manitoba
RNA-based systems, molecular machines, and bio-inspired devices are the future of the bioeconomy. Advancing these technologies from discovery to market can be elusive.
Accelerating scientific discoveries in natural and synthetic biology into deployable products and knowledge requires a collaborative and integrative ecosystem.
The success of RNA vaccines demonstrates that we’re in the golden age of mainstreaming synthetic biology and bio-inspired technologies. This achievement was, however, the culmination of decades of research coalescing under the pressure of the pandemic, and notably was brought to bear outside of Canada. This example highlights the collaborative eco-system needed to advance biotechnologies. An ecosystem that facilitates the interaction of start-ups, SMEs, larger industry, academia and government, and provides access to the equipment and talent available at universities is required. To address this urgent need for this type of innovation and discovery net-work in the prairies, the University of Manitoba recently launched a hub for the exploration of natural and synthetic biology, BioExM.
We are opening the door to partners from all sectors to work together to fast track innovations in synthetic biology and bioengineering through our integrated Learn, Design, Build and Test model.
BioExM – Creating a vision for biotechnology in the prairies
Drs. Hans-Joachim Wieden, Lead for BioSciences Entrepreneurship and Industry Partnerships, and Ned Budisa, Canada Research Chair in Chemical Synthetic Biology, were recently recruited to the Faculty of Science at the University of Manitoba and are leading this hub. We had the opportunity to virtually sit with Drs. Wieden and Budisa for a Q&A to hear more about the future of BioExM and its role in advancing biotechnology.
What was the inspiration behind the launch of BioExM?
Budisa: Although Canada is now investing in vaccine development and manufacturing, a lack of an existing framework for the advancement of vaccines meant we were left behind in the race for the COVID-19 vaccine. Here, we’re taking a more forward-looking approach by building on the critical mass of research expertise existing in the prairies in synthetic, structural and digital biology to provide biologically-based solutions to myriad challenges in diverse sectors such as agriculture, energy, and medicine.
What would be the benefit of accessing this new hub?
Budisa: Fundamental and cost barriers limit the participation of emerging companies and SMEs in the R&D enterprise. Effectively, we’re bringing partners together by lowering the access barrier and de-risking participation in research. We are opening the door to partners from all sectors to work together to fast-track innovations in synthetic biology and bioengineering through our integrated “Learn, Design, Build and Test” model.
How to accelerate scientific discovery into deployable products and knowledge?
Wieden: The Learn, Design, Build and Test model ensures industry can capitalize on the expertise of award-winning researchers, technologies, state-of-the-art equipment, and talent found at UM. Within this model, the discovery of natural biological processes will be accelerated by state-of-the-art technologies and instrumentation, these findings will be interpreted and analyzed (LEARN), which will instruct the (DESIGN) of experiments, technologies or applications. Further advancement is supported by the capacity to (BUILD) the necessary component e.g. genomes, proteins, etc., which will be characterized (TEST), enabling successful deployment. As discoveries and products advance to market, these can be fed back into the cycle and the next phase of analysis, ultimately lowering technology barriers and mainstreaming access to emerging bio-inspired technologies.
Why a discovery acceleration hub at an educational institution?
Wieden: How can you grow an emerging technology without a pool of well-trained potential employees? The UM is a research powerhouse with particular strength in emerging sectors of the molecular life sciences such as RNA-based technologies, synthetic biology, and bio(inspired) engineering. Students here are trained in these emerging trans-disciplinary areas. As we move forward, we envision a maker space where entrepreneurial students, SMEs, and start-ups can develop their ideas and tap into cutting-edge research. Why couldn’t the next “killer-app” be bio-engineered here in Manitoba?
What is the take-away message?
Wieden: We’re open for business and we are inviting our partners across all sectors to come Learn, Design, Build and Test with us.
The solution is in our biology
As a network for the exploration of natural and synthetic biology at the University of Manitoba, BioExM hosts a breadth of expertise in synthetic, structural and digital biology. From new approaches to drug design, to biosensors, environmental sustainability, and large data analysis our researchers are providing biology-based solutions to emerging challenges facing our communities and the world.
Re-imagining the genetic code for smart materials and sustainability
Synthetic protein production has the potential to revolutionize the way we make drugs, vaccines, fuels, and new materials. Although synthetic proteins can be produced by chemical synthesis and in vitro methods, these approaches are complex and produce low yields compared to the production in living cells. Based on an engineered orthogonal translation system in cells dedicated for site-specific incorporation synthetic amino acids, Dr. Ned Budisa has pioneered the production of synthetic proteins containing modified residues at predefined sites. He has incorporated more than 200 amino acids with different side-chain modifications into synthetic proteins using this approach. This expansion of the genetic code enables the possibility for many still unanticipated protein-based technologies Dr. Budisa has dedicated his time at the University of Manitoba in pursuit of applying his protein-based technologies to evolve enzymes and microbes for bioremediation of plastics and organic pollutants, to develop protein-based drug delivery systems, and to engineer biosensors and nanodevices for diagnostic purposes
Using an atomic level approach to predict small molecule design and activity
Computational chemistry approaches to small molecule drug design have been applied for decades, but traditional computational tools have lacked the power to successfully predict activity in light of the complexities of our biology. Dr. Rebecca Davis’ research is at the intersection of chemistry and biology and delves deep into the atomic level to investigate how small molecules invoke their activity based on their interactions with proteins. With this granular information, she then uses high-powered state-of-the-art computational approaches to predict features of other small molecule-protein binding interactions and energies to design improved drugs. With expertise in organic chemistry, Davis’s lab is then able to synthesize these newly improved compounds for experimental validation. This approach to studying small molecule interactions can be applied to a range of areas within and beyond medicine and Dr. Davis has been applying these methods to solve problems in antibiotic resistance, Gauche’s disease, and the toxicity of environmental pollutants.
Bringing diagnostics to the bedside with electrochemistry
Personalized medicine is the future of health care. We are already applying this approach for certain cancers where drugs are chosen based on the specific mutations in the cancer cells, but the time and cost to conduct this level of diagnostic is still a major hurdle for the widespread use of personalized medicine in a number of fields. In particular, the treatment of bacterial infections is often done empirically, meaning that the doctor prescribes an antibiotic based on symptoms alone. This leads not only to possible treatment failure but also contributes to the rise in multidrug-resistant bacteria. Dr. Sabine Kuss, an award-winning electrochemist, aims to reduce the time for diagnostics to a matter of minutes with the development of biosensors that can be incorporated into handheld devices for use in the clinic. Using electrochemistry, these sensors are able to detect substances that cross the outer layer of live bacteria and cancer cells. By detecting which substances, the bacteria or cancer cells expel, scientists can tell whether a cell is susceptible or resistant to a specific medication and therefore can rapidly select the most appropriate drug for treatment.
Developing efficient algorithms to tackle complex problems
As all areas of biological discovery continue to grow and advance, the ability to process and present the vast amounts of data produced has become a critical problem. Dr. Olivier Tremblay-Savard primarily conducts research in comparative genomics, a field where complex biological problems include distance calculations, reconstruction of ancestral genomes, and inferences of evolutionary patterns. Using an interdisciplinary approach involving computer science, biochemistry, microbiology, molecular biology, and evolutionary biology, Dr. Tremblay-Savard develops efficient algorithms to tackle these and other complex problems. With a background in algorithmic, theoretical computer science, human-computer interactions, and gamification, he is able to approach these problems from many different angles and is also able to create user-friendly, accessible, clear, and engaging software.
Predicting antibiotic activity with artificial intelligence
The search for novel antibiotic compounds has traditionally required testing millions of natural and synthetic compounds, which is a time-consuming and costly venture. Dr. Silvia Cardona is a microbiologist collaborating with Dr. Pingzhao Hu, a computer scientist, and Dr. Rebecca Davis, a chemist to develop artificial intelligence (AI)-driven tool to predict antibiotic activity in expansive virtual compound collections to screen for highly active molecules. Dr. Cardona’s unique platform integrates the global cellular response of bacteria to antibiotics with detailed descriptions of chemical structures and yields information on novel antibiotic mechanisms of action. Coupling high-throughput experimental data generation to AI-driven data modeling makes drug discovery automatic and fast.
Uncovering the principles of biomolecular design
Understanding the underlying design principles of biomolecular function enables rational design of new biomolecular machines, or modulating the performance of existing biomolecular machinery within the cell. The rational design of biomolecular function is, for example, of particular interest for the development of new antimicrobial strategies, whereas the modulation of existing machinery enables the construction of next-generation molecular tools such as highly specific biomolecular sensors. Dr. Hans-Joachim Wieden specializes in design-focused discovery research with particular emphasis on ribosome-dependent protein synthesis. The ribosome is a megadalton molecular machine that is composed of two types of biomolecules fundamental to life, RNA and proteins. The ribosome and its regulatory factors are at the center of the later steps of gene expression in all living cells. Dr. Wieden uses a multi-disciplinary approach combining classical preparative biochemistry and rapid-kinetics, with advanced structural biology (Cryo-EM) and computational techniques (Molecular Dynamics Simulations) to extract fundamental principles of biomolecular function and to describe, predict and manipulate their performance. This approach is therefore applicable for many biomolecular systems beyond the ribosome, truly enabling the molecular design of next-generation bio-inspired solutions from the ground up.
Leveraging non-coding RNA to forge new cancer therapeutics
RNA has been gaining traction as a promising molecule for not only vaccine development but also for therapeutic development. Dr. Sean McKenna seeks to understand the roles that non-coding RNA play in the regulation of human disease states, with a focus on cancer. He uses a combination of biochemistry, molecular biology, and cell biology to identify the biochemical pathways that these non-coding RNAs participate in, and the protein complexes that they regulate. Integration of synthetic biology approaches have allowed the addition of unconventional chemical groups to RNA. These modifications are unique to human cells and allow Dr. McKenna to specifically identify binding partners of non-coding RNA, regulate the levels of specific non-coding RNA, or visualize RNA in a cellular context. Therapeutic approaches with unconventional RNA modifications have the potential to specifically target the non-coding RNA involved in some of the lesser-studied cancer pathways opening new hope for treatment.
Delivering safe and specific pesticides
Most pesticides currently used in agriculture and urban environments are broad-spectrum in their activity and can cause serious adverse effects to non-target species. Dr. Steve Whyard is developing an RNA interference technology that applies double-stranded RNA (dsRNA) to knock down sequence-specific gene expression and offers a new generation of pesticides that are species-specific, and therefore do not adversely affect non-target species. Due to the ease by which new pesticidal RNAs can be developed, Dr. Whyard’s technology could be applied to a vast array of other pests and pathogens of crops, other pests of our homes and urban environments, and other food production systems. His research group is currently developing RNA-based pesticides to control specific disease-carrying mosquitoes, insect pests affecting canola crops, and fungal pathogens affecting several commercially important crops. As an extension of this work they are also investigating novel RNA delivery systems. As the RNA-based pesticides are readily biodegradable and so species-specific, they have the potential to be applied in many food production systems where chemical pesticides are not tolerated, either for health or environmental protection reasons.
Working with Canadian communities for environmental monitoring and bioremediation
Communities across Canada are experiencing the effects of industrial pollutants and climate change. To enable our communities to assess environmental parameters in the most efficient way, Drs. Jörg Stetefeld and Gregg Tomy, founders of the Centre for Oil and Gas Research and Development
(COGRAD), are developing and applying cutting-edge environmental monitoring tools, including gas chromatography-tandem mass spectrometry (GC-MS/MS) for detection of petroleum chemicals like polycyclic aromatic compounds (PACs), bioinspired monitoring and remediation tools, and eDNA metabarcoding approaches. Using a broad spectrum of world-class chemical analysis tools in conjunction with innovative applications in the field of bioremediation and monitoring, they are making discoveries across the country from projects in the Alberta Oil Sands to the Canadian Arctic in close collaborations with Environment and Climate Change Canada and members of several First Nation communities.
Notably, using black smoker originating from archaea bacteria nanotubes to detect and filter PAC compounds from the environment, they discovered a new class of PAC compounds in the Alberta Oil Sands, the halogenated PACs. Just recently they have started on an Artificial Intelligence-driven approach to detect PAC binding mechanisms in animal and human PAC receptor proteins. Their vision is to develop an algorithm that allows for an advanced risk assessment of these compounds.
