Terrence Donnelly Centre for Cellular and Biomolecular Research - Case for Support

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Leading the Way to a New Era in Human Health...... 2 The Promise of Personalized Medicine...................... 4 The Donnelly Centre.................................................... 6 Discovering the Cause of Human Disease................. 10 Advanced Diagnosis of Disease and Infection........... 12 Reversing Injuries and Disease................................... 14 Philanthropy and Scientific Discovery........................ 16 Giving Opportunities.................................................... 18 Conclusion................................................................... 20

No matter how long or short our lives may be, everyone everywhere yearns for a life that is free from the threat of major disease or the devastation of major injury. The only way that yearning can be satisfied is through research, research and more research.

Dr. Terrence Donnelly, C.M., O.Ont., LL.D. (Hon.)

LEADING THE WAY TO A NEW ERA IN HUMAN HEALTH If you compare the DNA of two different people, you will find about three million differences. This genetic variation governs how humans differ from one another—in our appearance, our personality and our innate abilities. Our genomes also determine what diseases we might get and how we respond to treatment.

All disease has a genetic basis, whether it arises through inherited or genetic changes that are induced through environmental influence or aging. Remarkably, the scientific community has only appreciated the degree of variation between individual genomes in the past decade. This amazing insight resulted from collaborations between engineers, chemists and biologists to develop new, efficient methods to decode or sequence genomes. Sequencing the first human genome took more than 10 years and $2.5 billion. Today, it can be achieved within days and for a few thousand dollars. This has opened the door onto a vast landscape of research opportunities that promise


greatly improved human health and development. Scientists must now decipher how the millions of genetic variations in our DNA manifest themselves, especially with respect to disease. This knowledge will lead the way to the much-anticipated era of personalized medicine. This is an entirely new paradigm in health that is built around each person’s unique genetic profile and physiology. It will transform many current approaches to diagnosis, intervention and treatment, and promises some of the most dramatic gains in human health and well-being since the advent of modern medicine.


To realize this vision, we must support unconventional thinking — these new insights into the human genome have shown that there are many fundamental principles about human biology that are simply not understood. We need environments where scientists are expected to be curious, to invent, to be driven to ask questions that are constantly evolving, and are unexpected and inspiring. This attitude defines the Terrence Donnelly Centre for Cellular and Biomolecular Research (The Donnelly Centre) which, only 10 years after its founding, is internationally recognized as a leader in post-genome biology. The Centre features renowned researchers and


their trainees from diverse fields working side-by-side within cutting-edge facilities. The result is a dynamic, inspiring ecosystem, ideally suited for scientific discovery and made even more powerful through its full integration within a globally-recognized health sciences research network. At this point in time, with so much opportunity for discovery, philanthropic support can be a catalyst that leads to critical scientific breakthroughs. Fundraising efforts for the Centre are an integral part of Boundless, the $2-billion campaign for the University of Toronto.


THE PROMISE OF PERSONALIZED MEDICINE Personalized health care will allow physicians to detect disease and halt its progress at the earliest stages. It will take into account your unique genetic makeup in order to develop the treatment plan that is best for you.

Imagine a world where our parents knew from early in life or even in utero that we are at risk for a brain disorder such as autism. With this knowledge, intervention can occur long before any symptoms are apparent — mitigating or even avoiding the disorder altogether. What if we are stricken with cancer? Imagine then that instead of the full-spectrum approach of chemotherapy, with its debilitating side-effects, that the disease could be precision-treated, using tailored antibodies that target our specific cancer.


Consider another scenario in which a loved one is on a waiting list for a desperately needed organ transplant. What if the organ could be regenerated using the person’s own cells, thereby also eliminating the risk of organ rejection? These are examples of the remarkable promise of personalized medicine. It is a vision of care in which doctors have the ability to predict and diagnose disease far in advance and are consequently able to intervene


much more effectively. Personalized medicine also encompasses the ability to treat injury and disease using methods that are less invasive and more precise than today’s surgery and drugs. This approach will employ therapies tailored to an individual’s genetic profile and targeted only at afflicted parts of the body. What stands between us and this goal of personalized medicine? Our researchers must determine which genetic


sequences are associated with which health outcomes in order to understand what goes wrong in cells that leads to disease. These are the big questions being addressed at the Donnelly Centre. As each foundational discovery is made, it kicks off subsequent advances and innovation by the entire health sciences sector. The result will be new drugs, patient therapies, medical devices and other applications that save and improve lives.


THE DONNELLY CENTRE The Donnelly Centre has emerged as one of the top research and educational institutes in the world, recognized for its leadership in uncovering basic principles in biology that have profound implications for human health.



The Donnelly Centre attracts top minds from fields such as medicine, engineering, cell biology, computer science, physics, chemistry, proteomics and functional genomics. The Centre’s approximately 35 principal investigators and 500 students, trainees and staff have a research agenda dedicated to basic science and pure discovery— an irresistible environment for brilliant, collaborative and unconventional researchers and students from around the world. This broad research program is the method most likely to transform human health.

one of the world’s leading research universities and home to Canada’s largest faculty of medicine.

The Donnelly Centre contributes to, and is integrated with, Toronto’s powerful cluster of biomedical companies. This network is anchored by the University of Toronto,

On the following pages, we showcase examples of the cutting-edge research ongoing in the Donnelly Centre.


These affiliations also support the Donnelly Centre as a premier educational destination for tomorrow’s health science leaders. The Centre’s bright, open concept design houses a vibrant training environment that brings together post-doctoral fellows and graduate students with esteemed faculty and is essential to the exchange of ideas across generations.



Supporting research at the Donnelly Centre is the best investment I have ever made in my life. The University of Toronto and the Donnelly Centre’s director, Dr. Brenda Andrews, have done a fabulous job of assembling an outstanding group of scientists who are producing world-class results that are making a difference in the lives of people in Canada and around the world. They are making medical breakthroughs that will permit humankind to advance in the fight against disease. Continued work is needed to discover the causes of disease and to learn how we can prevent people from getting sick. Basic scientific research is the only way we will be able to achieve this.


This is where we will find cures today’s doctors cannot even imagine. Dr. Terrence Donnelly, C.M., O.Ont., LL.D. (Hon.)


DISCOVERING THE CAUSE OF HUMAN DISEASE It is still early days in terms of understanding the connections between our genes and the causes of disease. The challenge stems from the fact that most common conditions, such as Alzheimer’s disease or cancer, are caused by mutations in more than one gene. Continued research in this area is key in the fight against the most harmful afflictions of our time. Donnelly Centre researchers are conducting basic research to understand how cells, tissues and organs work in order to shed light on how normal processes are subverted in disease.

UNDERSTANDING HUMAN BIOLOGY USING YEAST Yeast is a simple, single-celled organism that shares a basic biology with human cells. This shared biology has been dramatically highlighted over the years by discoveries about the basic workings of the cell for which yeast researchers have been awarded the Nobel Prize, among other honours. Yet, even though yeast cells have a relatively simple genetic manual —about one quarter of the human complement —scientists have been stymied by the incredible complexity of biological systems, and have been unable to understand how genes work together to determine how yeast or human cells function. Thanks to prototype, state-of-the-art robotic technology, Donnelly Centre researchers were able to study in exquisite detail how all genes in the yeast cell work together to underpin a cell’s survival and function. These breakthrough insights into the basic wiring of a cell are necessary if we are to understand


what makes human cells healthy and what goes wrong when disease strikes. The work in yeast has inspired new collaborations in the Donnelly Centre, applying powerful robotic platforms to study cancer cells in previously unimaginable detail to find better ways of attacking them. Lead researchers

Drs. Brenda Andrews, Charles Boone, Timothy Hughes and Jason Moffat

This image illustrates a correlation-based network connecting genes with similar genetic interaction profiles in the budding yeast, Saccharomyces cerevisiae.


Digital map representing protein interactions in a cell



Worms are powerful models for human genetics because they’re relatively simple animals, made out of only 1,000 cells. Yet, like humans, they have about 20,000 genes, half of which are closely matched to ours. What’s more, worms can be experimentally manipulated on a scale that surpasses anything that is feasible for larger animal models.

Instructions for making our bodies are encoded in around 20,000 genes and executed by hundreds of thousands of molecules in our cells. However, scientists still don’t understand how the many gene products made in our cells fit together to make a healthy brain or a weak heart.

Donnelly researchers are pioneers in building robotic platforms to harness this potential for new discovery. By studying how thousands of genes and drugs work together in the worm, they are gaining valuable insights into basic principles that underlie the vastly more complex human biology. This process is helping them predict how inherited mutations influence not only the risk of disease, but also its severity, as well as find new drugs to treat conditions such as neurodegeneration and mood disorders.

Donnelly Centre researchers have developed computerbased algorithms that can make sense of a massive amount of medical and genomic data, allowing them to “look under the hood” of our bodies like never before to see how all the parts fit together in different people. This research will yield personalized blueprints to guide medical decisions such as diagnosis, prognosis and treatment, and has already proven successful in generating the first potential targeted therapy for a childhood brain cancer. Lead researchers

Lead researchers

Drs. Andrew Fraser and Peter Roy


Drs. Gary Bader, Frederick Roth, Quaid Morris and Timothy Hughes


ADVANCED DIAGNOSIS OF DISEASE AND INFECTION Across the landscape of human health, researchers and practitioners have shown time and time again that early intervention is critical in mitigating or avoiding a host of diseases including diabetes, cancer and heart disease. Early intervention is, of course, contingent upon early detection. Delivering powerful predictive and diagnostic capacity to health-care professionals is a cornerstone of personalized medicine and a key benefit accruing from the basic science research conducted at the Donnelly Centre. UNRAVELLING THE COMPLEXITY OF BRAIN DISORDERS


Complex brain disorders, such as autism or schizophrenia, remain a mystery because they are caused by mutations in many genes, whose ramifications lie hidden in early events of brain development. But if physicians could diagnose and treat such disorders early, they would be able to help affected individuals improve their behavioural and social outcomes.

All cells in our bodies have identical genes, yet clearly cells that make up the heart or liver carry out different functions — keep our blood pumping and degrade toxins, respectively. What makes cells able to do such different tasks is the set of genes that they have switched on. When this process goes haywire, cells can lose their identity, and this often leads to disease such as cancer. The rules for switching genes on or off are written in the genome, but finding and interpreting them has been difficult.

Thanks to new genetic and computational tools developed at the Donnelly Centre, researchers now have a better grasp on these previously intractable disorders. Donnelly Centre researchers are working closely with collaborators at the Hospital for Sick Children and Mount Sinai Hospital to better understand key genes and molecular mechanisms involved in autism. These studies are illuminating new biomarkers and common molecular changes in this disorder that represent potential targets for diagnosis and treatment.

Thanks to the collaborative approach, Donnelly Centre researchers have made huge strides in understanding how cells read the genome. The use of model organisms, including both yeast and human cells, combined with high-throughput technologies and the latest computational systems, has led to major insights that will allow scientists to predict gene activity in different scenarios. This knowledge is key if we are to understand the identity of each cell and even bring diseased cells back into their original states.

Lead researchers

Drs. Benjamin Blencowe and Brendan Frey

Lead researchers

Drs. Timothy Hughes and Quaid Morris



TINY DETECTORS FOR BIG PROBLEMS A nanometre is a million times smaller than the diameter of a human hair! Nonetheless, technologies that operate on micro- and nano-scales have emerged as one of our biggest weapons in the fight against disease. These devices can pick out molecules in blood, urine and tumours and tell the doctor what condition a patient has. But they are still too costly to be part of everyday life. Researchers at the Donnelly Centre are working on perfecting these devices so that they can be used by everyone in the world. This involves the assembly of nanotechnology parts and/or microfluidic systems into hand-held, inexpensive diagnostic equipment. So far, the

team at the Donnelly Centre has applied this technology to detect a wide range of disease, including cancer, heart disease and infectious diseases such as HIV-AIDS, hepatitis B and C, and rubella. These devices could be no more exotic than a common smartphone and will have particular benefits for remote populations far from specialists and other clinical services. For example, the team is getting ready to test one such device that they built for its ability to diagnose rubella and measles in refugee sites in Kenya. Lead researchers

Drs. Warren Chan and Aaron Wheeler

Laboratory research— nanotechnology and the use of quantum dots in biomedical applications



REVERSING INJURIES AND DISEASE Another important aspect of personalized medicine is precision therapy based on each person’s genetic profile and focused solely on afflicted areas of the body. Discoveries in this area by Donnelly researchers will lessen trauma to the body caused by invasive medical responses to serious illness and organ failure. These treatments will not only mitigate stress and suffering but also reduce the financial strain on our health-care system of many current treatment methods. ANTIBODIES MADE TO ORDER


Produced naturally by our bodies, antibodies help us fight infections. Man-made antibodies have the potential to revolutionize medicine because they can be designed to attack any disease agent, including, for example, molecules that help cancers grow. However, real progress has been slow because making antibodies has been costly and time-consuming.

Stem cells are key to regenerative medicine because they can self-renew and turn into any cell type, such as those that make up the heart or the brain. While scientists have made huge strides in creating different kinds of cells and tissues from stem cells in a lab, generating clinically useful amounts of stem cells remains a challenge.

Donnelly Centre researchers have developed a powerful antibody-engineering pipeline to build vast collections of synthetic antibodies faster and on an unprecedented scale. These high-quality antibodies are not only invaluable tools for further research into cellular function, but they also have strong diagnostic and therapeutic potential. The goal is to find drugs with minimal sideeffects by identifying antibodies that block specific diseases such as cancer and diabetes.

Donnelly researchers are focused on this issue with cutting-edge technology that uses bioreactors to grow stem cells under robust conditions in large numbers. Their main focus is to produce blood, pancreatic and heart cells in sufficient numbers to be used for drug discovery, as well as to potentially treat blood disorders or diabetes and repair heart damage. Lead researcher

Dr. Peter Zandstra

Lead researchers

Drs. Sachdev Sidhu and Jason Moffat



A DELIVERY SYSTEM FOR HEALING Advances in stem cell biology hold great promise for generating replacement tissues and organs to treat conditions such as blindness, diabetes and stroke. But getting the right cells for transplant and having them survive and integrate into the neural circuitry after transplantation are significant challenges.

Donnelly Centre researchers have designed strategies to program stem cells for transplantation. They have developed innovative gel-like biomaterials, called hydrogels, which enhance cell survival and integration into the transplant site, thereby promoting tissue regeneration and functional recovery. In animal models, this has already been shown to partially reverse blindness and help the brain recover from stroke. These findings are part of ongoing efforts to develop new therapies to repair nerve damage caused by a disease or injury. Lead researchers

Drs. Molly Shoichet, Cindi Morshead and Derek van der Kooy



PHILANTHROPY AND SCIENTIFIC DISCOVERY Top scientists and leading philanthropists share similar characteristics, especially a desire to confront life’s most pressing challenges and to forge positive, lasting change. It’s a world view defined by vision, knowledge, perseverance, resourcefulness and recognition on the part of both philanthropists and scientists that they are uniquely positioned and well-equipped to better our world.

These are the qualities needed to undertake successful research because it is by definition a venture into the unknown that may lead to entirely new worlds of understanding. Increasingly, this vision is found within a committed and knowledgeable donor who recognizes the potential of a research effort from its earliest days. A philanthropic investment in fundamental basic science not only allows research teams to immediately mobilize and focus their work, it enables scientists to obtain pilot data they can use to pursue additional grant funding, thus multiplying the impact of this donation. The benefits of this growing partnership between public funds, private philanthropy and the scientific community are deep and broad. Donnelly Centre investigators are not only basic scientists who are driven by big health-relevant


questions, but also entrepreneurs, technology developers and inventors. Technology development has driven all major advances in how we do biomedical research in the past decade, and breakthroughs in basic science labs have had an astounding catalytic effect, enabling innovative research in labs and hospitals around the world. Such developments are a pillar of Canadian health, prosperity and innovation. To remain at the cutting edge, research projects in Donnelly labs, as well as Donnelly trainees and investigators, require consistent support that rises above political trends or fluctuating economic conditions. More than ever, informed and engaged donors are the source of this unwavering commitment, driving successful research efforts— especially at their earliest, unproven stage.


This image illustrates yeast cells growing in a laboratory dish. Each set of cells carries a mutation in a different gene, allowing scientists to elucidate what each gene does in a cell.



GIVING OPPORTUNITIES Every researcher at the Donnelly Centre will tell you that their work is accelerated because of the uniquely powerful ecosystem of discovery and innovation at the Centre. The Centre’s open concept space, state-of-theart infrastructure, and its sheer concentration of leading thinkers result in inspired and collaborative research efforts. Nurturing and building this remarkable and results-driven community is our most urgent priority.

Funding for leadership positions will ensure that we continue to boast some of the top minds from around the world in key positions. ––


e seek support to create an endowed Chair for the W Director of the Donnelly Centre. This funding will ensure that the Donnelly Centre continues to be directed by a leading global researcher and visionary administrator who can drive coordinated research and academic strategies ($5 million). L eadership support will also create several endowed Chairs in key areas of research activity ($3 million each).

We also require funding for an Innovation Fund ($12 million) that will allow the Donnelly Centre to respond nimbly to emerging research directions and to support promising investigators at the outset of their careers — a particularly necessary investment considering the urgency of the research challenges and the need for research continuity across generations. The Innovation Fund will support: ––

A Catalyst Award to inspire groundbreaking research ideas;


ew Innovator Training Awards to attract N quantitative scientists to biology, including physicists, mathematicians and computer scientists; and


A Think Tank that will extend the Donnelly Centre’s international stature and influence by inviting global scholars to twice-yearly conferences on interdisciplinary biomedical research.

ifts to the Donnelly Centre are an integral part G of Boundless, the $2-billion campaign for the University of Toronto.



RECOGNITION AND ENGAGEMENT We will be delighted to work with donors to recognize their generosity appropriately and to inspire others in the community. Options include naming of faculty positions, awards and physical space, in accordance with University policy. The Terrence Donnelly Centre for Cellular and Biomolecular Research is committed to keeping our donor community informed and engaged regarding research progress and events.



CONCLUSION This is an incredibly exciting time in biomedical research. The mapping of the human genome was like charting the coastline of a vast and unknown land. We are now venturing into the interior, where every step we take is sheer discovery, breaking entirely new ground. At the end point of this journey is a new world of personalized medicine where much of the suffering and loss we now routinely endure through disease and injury will be greatly reduced or eliminated altogether.

This new era of personalized, genomic medicine offers a remarkable opportunity for visionary philanthropists to change lives across entire populations. The Donnelly Centre is at the vanguard of forging a precise understanding of the genetic mechanisms of disease and healing, informing our approach to human health from this point forward. This is not incremental progress in a specific area of concern. This is a broad-based endeavour that is no less than historic in its scope, aspiration and significance. At this critical stage when


we are exploring so many fundamental areas through basic science research, committed philanthropists can play an absolutely essential role. Thank you for your interest in the Donnelly Centre. We invite you to learn more and to lend your energy and resources to the goal of greatly reducing the burden of disease and injury in a new era of personalized medicine.


This image illustrates human stem cells growing in a laboratory dish. Stem cells can turn into any cell type and could be used to replenish or repair damaged tissues or organs.



Michelle Coutinho Senior Development Officer Office of Advancement Faculty of Medicine University of Toronto 6 Queen’s Park Crescent Toronto, Ontario M5S 3H2 Canada Tel: 416-946-8103 michelle.coutinho@utoronto.ca thedonnellycentre.utoronto.ca