Biological Resilience Initiative

Antimicrobial resistance (AMR) is a pressing issue threatening our ability to combat infections caused by bacteria, parasites, viruses, and fungi. The World Health Organization has flagged AMR as a top global public health concern, as it not only leads to severe illness and death but also imposes significant economic burdens due to prolonged treatments and increased healthcare costs. LSI researchers are actively tackling this challenge by investigating the mechanisms behind AMR and developing new strategies to overcome it. Using cutting-edge techniques such as advanced structural biology in the ASTRID core, high-throughput screening in the Biofactorial core, and microbial genetics analyzed in the Bioinformatics core, they aim to understand how pathogens evade our immune system and identify potential targets for new antimicrobial drugs.

Collaborative efforts within and beyond the LSI have led to promising discoveries, including novel therapies like host-directed therapies (HDTs) that target human cells to circumvent AMR. Through multidisciplinary approaches spanning different scales of research, LSI scientists are at the forefront of finding innovative solutions to combat AMR and develop new treatments for drug-resistant infections.

Cancer, a leading cause of global mortality, arises from disruptions across various biological levels, including genes, cells, and tissues. LSI researchers specialize in uncovering the fundamental mechanisms behind cancer development, utilizing core services like Bioinformatics for genome-level studies and LSI IMAGING for cellular investigations. Their focus extends to understanding how environmental factors, such as diet and aging, impact gene regulation through epigenetic changes, with the aim of identifying new therapeutic targets.

LSI's interdisciplinary approach extends to systems-level inquiries, exploring topics such as cancer metabolism and the resilience of the immune system against tumor formation. Collaborative efforts, including therapeutic strategies like immuno-oncology through ubcFLOW, aim to translate these findings into effective treatments. By addressing fundamental questions and leveraging advanced technologies, LSI researchers strive to improve cancer outcomes and advance our understanding of this complex disease.

The immune system acts as our body's defense mechanism against infections and diseases like cancer. However, when this system is thrown off balance, it can lead to autoimmune disorders or severe inflammatory responses, as seen in conditions like COVID-19. To better understand and harness the immune system for therapeutic purposes, LSI researchers utilize advanced tools and technologies provided by core services like ubcFLOW, LSI IMAGING, Proteomics and Metabolomics, and Bioinformatics. These analyses are crucial for developing vaccines and immunomodulatory treatments, particularly in the context of diseases like COVID-19, where understanding immune responses is vital for tailoring effective interventions.

Through collaborations and interdisciplinary approaches, LSI researchers aim to unravel the complexities of immune responses at different scales, from atomic to systems levels. This includes studying how factors like age, sex, genetics, and environmental influences impact immune equilibrium and responses. By employing cutting-edge techniques such as single-cell RNA sequencing and protein profiling, researchers can delve into the intricacies of immune function and develop novel strategies for treating autoimmune disorders and enhancing vaccine efficacy. These efforts are essential for addressing the grand challenge of understanding and manipulating immune resilience for improved health outcomes.

Common chronic diseases such as cardiovascular diseases, neurodegenerative disorders, osteoporosis, and metabolic diseases like diabetes and obesity often stem from an age-related decline in the body's ability to maintain balance. These conditions, which frequently overlap and exacerbate each other, currently lack effective treatments targeting their underlying metabolic defects. LSI researchers are dedicated to laying the groundwork for future therapies that modify the course of these diseases by addressing metabolic dysfunctions. Leveraging core services like ubcFLOW for diagnosing immune senescence and Bioinformatics for data analysis, they investigate the intricate connections between metabolism, aging, and immunity, aiming to uncover novel therapeutic targets.

Through interdisciplinary collaborations and utilizing advanced techniques such as transcriptomics and proteomics, LSI researchers delve into the underlying mechanisms of aging-related diseases across various model systems, including fruit flies, worms, genetically engineered mice, and human tissue organoids. By comparing molecular aging pathways across these models and correlating findings with human genomic data, they strive to identify conserved targets for intervention. Additionally, Stem Cell and Genome Engineering facilitates the creation of human cell-derived models to test specific pathways involved in aging. LSI researchers are at the forefront of developing cell replacement and gene therapies for these diseases, from foundational research to leading clinical trials. Through these concerted efforts, LSI aims to advance our understanding of age-related diseases and develop innovative therapies to improve health outcomes.

Human resilience on Earth relies on sustainable methods of extracting energy and materials from our environment while minimizing environmental impact. To achieve this, LSI researchers tap into the vast genomic diversity found in microbial communities, facilitated by the powerful tools of the Bioinformatics core. These microbial genomes, containing an immense amount of information accumulated over billions of years, provide the foundation for biological resilience in bacterial populations and drive energy and material transformations crucial for sustainability.

The Grand Challenge ahead involves leveraging this genomic diversity to engineer microbial strains and communities for various applications, from lignin valorization to carbon capture, with the aim of developing innovative biotechnologies. Using advanced techniques offered by the Biofactorial and LSI IMAGING cores, researchers design, build, and test engineered microbial systems to address environmental, industrial, and health-related challenges. By reconstructing microbial networks and understanding complex microbial communities, predictive models and monitoring tools can be developed, paving the way for sustainable solutions to pressing global issues like climate change.

LSI researchers, spanning diverse areas from environmental genomics to bacterial metabolism, collaborate to unlock the potential of microbial systems. Through characterizing enzymes, understanding microbial communities, and studying bacterial behaviors, they aim to deepen our understanding of Earth's biogeochemical cycles and develop resilient solutions for a circular bio-economy. Utilizing core services like the Proteomics and Metabolomics Core, researchers harness the power of microbial biology to drive sustainable innovation and address the challenges of the 21st century.

Molecular resilience explores how proteins and other fundamental biomolecules withstand and adapt to change—insights that are essential for understanding evolution at the smallest scale and for designing targeted therapies.

Researchers at the LSI are investigating the structural and functional resilience of molecules involved in human health and disease. This includes studying proteins critical to cellular function as well as those hijacked by pathogens. State-of-the-art core facilities such as the ASTRID and protein and vector engineering provide the tools to visualize these molecules with atomic precision.

Advanced techniques like cryo-electron microscopy, X-ray crystallography, and nuclear magnetic resonance are used to reveal the architecture of disease-relevant proteins. Complementary biophysical methods, including electrophysiology, help connect molecular structure to function—linking molecular dynamics to broader cellular processes.

Labs working at this scale address a wide range of scientific questions, contributing significantly to Grand Challenges in understanding disease mechanisms and developing innovative treatments.

Genetic, genomic, and epigenetic resilience underpin the ability of cells, organisms, and communities to rapidly adapt to changing conditions and transmit information across generations—driving both short-term adaptation and long-term evolution.

At the LSI, researchers investigate these mechanisms to better understand processes such as cancer evolution and stem cell differentiation. For example, by guiding human stem cells to form organoids that mimic real organs, scientists gain insights into tissue development and disease. Studying how cancer cells evolve within their environment could reveal new strategies for prevention and treatment.

This research deepens our understanding of gene regulation and inheritance and supports the development of therapies for a wide range of diseases. LSI's core facilities provide critical infrastructure: the Bioinformatics and Proteomics and Metabolomics cores enable analysis of genetic, protein, and metabolic data; the Stem Cell and Genome Engineering core allows for precise manipulation of genetic material; and the Biofactorial core supports genome-wide screening.

Labs working in this space play a central role in addressing complex scientific questions, particularly those related to disease mechanisms and therapeutic development.

Cellular resilience refers to the ability of individual cells and cell networks to adapt and maintain their functions within an organism. For example, resilient immune cells support the body’s defenses, while the plasticity of neurons—through the continuous formation and pruning of connections—shapes memory, emotional regulation, and responses to trauma.

Research at this scale explores fundamental aspects of cell biology, including cell division, structural integrity, signaling, morphology, and responses to changing environments. These processes are studied across diverse cell types, such as immune cells, neurons, and cancer cells.

To investigate cellular resilience, researchers employ advanced techniques like flow cytometry, high-resolution imaging, and electrophysiology. This work is supported by key resources, including the Bioinformatics and the Stem Cell and Genome Engineering cores, which enables the creation of human cell and tissue models relevant for clinical research.

Labs focused on cellular resilience are vital to tackling major scientific challenges, particularly in understanding disease and informing the development of targeted treatments.

Organism and system resilience describe how humans, animals, and microorganisms adapt to internal and external pressures—maintaining physiological balance and metabolic function across all life stages and sexes. Research in this area explores animal physiology, stress adaptation, tissue regeneration, and behavior.

The BRI leverages cutting-edge facilities like the Centre for Disease Modelling and specialized cores including the Stem Cell and Genome Engineering Core, ubcFLOW, and the LSI IMAGING. These resources support studies across a range of model organisms—from simple systems like Drosophila and C. elegans to complex mammalian models such as mice and rats. Insights gained are translated to human physiology through patient studies and engineered organoids.

Understanding disease mechanisms at this level requires integrated physiological approaches that consider the full spectrum of cellular and organ system interactions, including the critical role of biological sex differences. This holistic perspective captures individual variation, which is vital to understanding resilience at the population level.

Labs working at this scale are pivotal in advancing our understanding of organismal resilience and disease mechanisms.

Ecosystem resilience refers to how communities of organisms adapt and thrive through complex interactions—such as the delicate balance between human health and the microbiome, both within and beyond our bodies. At LSI, researchers study the resilience of microbial communities in diverse environments, including the gut and in the context of pathogen interactions, with a particular focus on antimicrobial resistance.

Their work deepens our understanding of host-pathogen dynamics and informs strategies for managing infectious diseases. To support this research, LSI scientists employ advanced tools such as single-cell genome sequencing and biosensors for environmental monitoring. They also draw on LSI core services including the Bioinformatics, Biofactorial, ASTRID, and Proteomics and Metabolomics Cores.

By investigating these complex systems, LSI labs play a critical role in tackling major scientific challenges—especially in understanding disease mechanisms and developing new treatments.