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Fiber Optic Nucleic Acid (FONA) biosensor based gene profiling

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Overview

DNA and its close relative, RNA, (both are called nucleic acids) carry the code of life in all of Nature’s creatures. By studying nucleic acids scientists can learn a great deal about human genetic diseases, and disease-causing viruses and micro-organisms. Nucleic acids are also important in environmental, defence, veterinary and agricultural applications. For all of these studies, scientists need to measure very accurately the amount of nucleic acids in a sample. Current methods have defects and we need new ones with fewer limitations.

The goal of this project was to develop a new kind of nucleic acid sensor (a “biosensor”) that is reusable, sturdy, rapid, accurate, selective, sensitive and cheap. We approached this by putting together a team that included medical geneticists, chemists, molecular biologists, engineers and computer scientists to work together to develop a new instrument.

It is based on the idea that certain chemical probes can detect specific stretches of DNA or RNA when attached to the surface of optical fibres. When the DNA or RNA to be detected is tagged with a light-emitting substance and binds to the optical fibre, it emits light that travels through the fibre and can be measured very accurately. Each measurement requires only a few minutes and the biosensor can be reused at least 100 times. We demonstrated the value of this new instrument by evaluating DNA that is associated with Spinal Muscular Atrophy, a very severe childhood genetic condition.

Development and applications of functional genomics technologies

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Overview

The Human Genome Project documents the complete DNA sequence, not only of humans, but of over 300 other organisms, with more to come. The next step is to turn this wealth of information into useful knowledge so that it can be applied to medical and biological advances. This kind of research is called “functional genomics” and it seeks to learn how genetic information coded in DNA directs all the workings of a living organism.

It is well known that advancements in new fields of science—such as functional genomics—depend on new technology. The goal of our research was to develop new techniques and measuring instruments for functional genomics, and to apply them to basic research and clinical studies. Our focus was on a new technology called DNA micro-arrays. This is a method of measuring with great accuracy and acute sensitivity the read-out from each individual gene in any organism. In order to improve this technology, we brought together a team of experts in biology, computer science, informatics and engineering to work in one of the World’s largest micro-array production and analysis programs at the University Health Network.

Our technical developments in DNA micro-arrays include the following: miniaturization to reduce the cost and complexity of experiments; automation of micro-array fabrication; new robots; increased rapidity of data collection; and better reliability of results. One of our robot designs is now sold commercially. We have developed better array design through the use of computational algorithms, more efficient storage and recovery of data from DNA microarray experiments, and better ways to compare our data with other researchers in the world. We have begun to use micro-arrays to study the expression of genes in children’s leukemia,ovarian and prostate cancer, cancer of the kidney, and heart disease. We provide DNA micro-arrays, training and support to over 300 research laboratories in 27 countries.

Outcomes

  • A robot design that is now sold commercially.
  • Number of research personnel employed by the project: 40
  • Number of peer reviewed publications published: 44 plus 1 book, 3 book chapters and 87 invited presentations Resources generated: 5 new devices, 1 reagent and 1 diagnostic marker; tens of thousands of DNA micro-arrays for researchers in Canada and abroad.
  • Number of public outreach events held: 22, including lectures, newspaper, magazine and TV articles, and public lectures.

Bridging the emerging genomics divide

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Overview

This is a stand-alone GE3LS project.

While life expectancies in industrialized countries are about 80 years and rising, in some developing countries, especially due to HIV/AIDS in sub-Saharan Africa, life expectancies are 40 years and falling. Inequalities in knowledge underlie these differences in health.

We have contributed to reducing these inequalities by examining the ethical, environmental, legal and social implications of advances in biotechnology and genomics.

We studied ethical questions faced by biotechnology companies and how they deal with them; our aim is to encourage companies to adopt suitable ethical policies. We led in writing a proposal for the Canadian government to guide its strategy for development of genomics and biotechnology; this has had an important effect on federal policy. We were a major contributor to the Genomics and Nanotechnology Working Group of the United Nations Science and Technology Task Force; this report was distributed all over the world. We led in the creation of a report which pointed out that in guarding against biological terrorism we should not undermine our ability to apply genomics for social benefit, especially in developing countries; the United Nations recommendations for a counter-terrorism strategy included reference to these conclusions.

We conducted courses in five regions of the developing world, with 232 participants from 58 countries, to help these countries shape policies in genomics and public health. We produced ethical guidelines for research, development, regulation and commercial use of nutritional-genomics and transgenic food products.

Outcomes

  • Reports and articles that address world-wide biotechnology issues.
  • Number of research personnel employed by the project: 5 graduate students, 2 post-doctoral fellows, 19 research associates and assistants, and 12 undergraduate students.
  • Number of peer reviewed publications published: 17, plus 12 books and monographs, and 5 book chapters.
  • Number of public outreach events held: 49 lectures, 1 public forum, media coverage – 118.
  • Co-funders: International Development Research Centre, National Institutes of Health, Indian Council for Medical Research, University of Guelph, Merck Frosst, Ontario Centre for Agricultural Genomics, World Health Organization (EMRO), United Nations University (BIOLAC), Pan American Health Organization and the Keck Graduate Institute.