Archives for September 2015

Understanding cancer causing cells

Every organ and type of tissue in the body contains a small number of what scientists call “adult” or “tissue” stem cells. Since most cells in the body live for just a short time, the body needs to keep making new cells to replace them. Adult stem cells ensure a continuous supply of new cells to replace old cells that wear out or are destroyed.

Cancer stem cells are the small number of cells within a tumour that drive the tumours growth, much in the same way cell stems create new cells, only in tumours the cells are cancerous.

The Challenge

  • Brain tumours, breast cancer and leukemias are among the most common and lethal cancers that affect Canadians
  • Current treatments are often ineffective because they do not target the rare cancer initiating cells – also known as cancer stem cells – that are responsible for tumour growth and spread
  • Better understanding is essential to the development of new and more effective anti-cancer therapies

The Research Solution

  • Ontario is a hot bed for cancer stem cell research. In fact, the cancer stem cells involved in leukemia, colon and brain tumours, were discovered right here in this province
  • New tools and technologies are being developed that can quickly scan cells and identify the start of diseases, helping with early disease diagnoses. These tools also allow for quick tissue sample analysis, enabling better monitoring of the treatment to assess whether it’s working and allow changes along the way
  • Ontarian researchers also received significant funding in 2009 through joint projects with researchers in California to look at the development of new drugs to treat leukemia and cancer-initiating cells in solid tumour cancers

Successes to date and potential impact

  • Research has led to the development of a new technique to grow cancer stem cells in the lab, facilitating international research in this area
  • Researchers working in this area identified a population of colon cancer stem cells, improving understanding of the disease and helping to better research ways to treat, or even prevent it
  • A new mouse model was developed for leukemia that can be used to identify human leukemia stem cells and study how these cells change as the disease progresses
  • More effective therapies as a result of better understanding and research would improve outcomes for the 174,000 Canadians diagnosed annually with cancer and help reduce the 76,000 deaths that occur annually

Integrated GE3LS Research: Attitudes of Adults and Adolescents to Predictive Genetic Testing for Diabetes

Investigating genome-environment interactions in diabetes

Type 1 diabetes is a disease in which the pancreas does not produce insulin, resulting in glucose accumulation in the blood instead of being used for energy.

The Challenge

Type 1 Diabetes (T1D) is a complex disease often arising in childhood in which the immune system destroys the insulin producing cells of the pancreas. Insulin is a crucial hormone in sugar and fat metabolism. Despite insulin therapy, T1D greatly increases the probability of heart attack, stroke, blindness and limb amputation, as well as shortened life expectancy.

  • Canada has the third largest incidence of T1D in the world, affecting some 200,000 Canadians, including 45,000 – 90,000 Ontarians
  • Ontario spends $5 billion a year on diabetes and associated conditions

The Research Solution

T1D is caused by multiple genetic risk factors and currently unknown environmental factors. Now an innovative research project is investigating the interactions of genetic risks and environmental factors underlying T1D.

Dr. Jayne Danska, Senior Scientist at Toronto’s Hospital for Sick Children and Professor in the Faculty of Medicine at the University of Toronto, and Dr. Andrew Macpherson, Canada Research Chair in mucosal immunology at McMaster University, are involved in a project that aims to understand how genetics can be used to control T1D in humans and rodent models. They will also study how exposure to common intestinal bacteria affects the development of the immune system and how such exposures affect the probability that people at genetic risk of T1D will develop the disease.

This project is expected to discover new genetic markers and identify environmental exposures that increase T1D risk, with the long-term aim of reducing disease risks through therapeutic intervention.

Successes to date

Several genes involved in diabetes have been discovered in tests carried out with mice. These tests have identified potential ways to help improve the immune systems in people with diabetes

The tests with mice has led to the building of a unique germ-free mouse facility in Toronto – one of only two in North America – that enables genomic analysis of animals with specific bacterial exposures under controlled conditions. This facility with its state-of-the-art technology will speed up research into diabetes and help discoveries be made quicker

This research is making great leaps towards reaching the ultimate goal of understanding how T1D is affected by environmental conditions, and armed with this understanding, researchers will be able to predict the body’s immune systems reaction to various treatments and environments, and even manipulate environmental factors to block or stop the development of the condition.

Associated Integrated GE3LS Research Project: Attitudes of Adults and Adolescents to Predictive Genetic Testing for Diabetes

Cleaning up contaminated water

Challenge
Water contaminants can lead to debilitating and deadly diseases such as dengue fever, cholera, dysentery, and diarrhea. More than a billion people worldwide have no access to a decent water supply. As a result, unsafe water, poor sanitation and hygiene are the leading causes of death in the developing world. In fact, the majority of illnesses in developing countries are caused by poor water and sanitation conditions.

Genomics solution
DNA-based technologies can quickly and accurately detect pathogens in a water supply, identifying unsafe water before it can make people sick. KB-1 is a value-recovery tool for contaminated groundwater. KB-1 can be injected into an area contaminated with trichloroethene (TCE) next to a river. Within 6 months, 98% of the estimated TCE mass was removed. It is the most widely used bioaugmentation culture used in the world for dechlorination. These versatile technologies can be adapted to identify a variety of contaminants, and are suitable for the unique conditions of developing countries.

Impact
Cleaning up contaminated water has an impact on human health. The rapid increases in population in developing countries & major urban centers will influence major investments for water and wastewater treatment needs and will drive water recycling and re-use.
KB-1 is currently being marketed and sold by SiREM. It has been translated from lab to marketplace.

KB-1 was discovered by Dr. Elizabeth Edwards (University of Toronto) and is now marketed and sold by SiREM. Dr. Edwards also leads the BEEM project, which aims to accelerate discovery and characterization of microbial consortia (KB-1 and others).

GAPP project description – Scale-up of bioaugmentation cultures and development of delivery strategies and monitoring tools for anaerobic benzene and alkylbenzene bioremediation

Making every species count

DNA barcoding is the use of short stretches if DNA to identify species. Making reliable and rapid species identification is essential to combating many of the threats facing our environment.

The Challenge

  • Climate change, invasive species migration and globalization of trade threaten ecosystems and biodiversity around the world
  • Pest damage to agricultural crops costs farmers the equivalent of billions of dollars each year, and leads to food shortage

The Research Solution

  • Dr. Paul Hebert’s International Barcode of Life (iBOL) project is working towards cataloging the world’s biodiversity by building a DNA barcode database
  • With research teams in 25 countries across the globe, Dr. Hebert is aiming to build a public resource with DNA barcodes from five million speciments representing at least 500,000 species over five years

How DNA barcoding will impact our world

New practical applications are constantly emerging, indicating limitless potential for iBOL’s growing digital reference library of DNA barcodes to impact on the way we live and interact with the world around us:

  • The ability to identify mosquitoes will help public health authorities to control the spread of diseases like the West Nile virus, malaria and yellow fever
  • Border control officials will be able to spot invasive species and fight the trade in endangered plants and animals
  • Early identification and control of invasive species will save the forestry and agricultural industries billions in lost production
  • Health care workers will be able to identify and control the organisms that make us sick as well as the vectors that spread disease
  • Animal feed will be tested for banned substances such as those that cause diseases like BSE
  • Water authorities will be able to monitor the health of our oceans, lakes and rivers, and the quality of our drinking water
  • Consumers will be able to check fish and other food products to ensure that what they are buying is what is advertised

Successes to date

  • Nearly ¾ of a million DNA barcodes sequenced worldwide to date
  • Dr. Hebert and his team at the Biodiversity Institute of Ontario are recognized as world-leaders in DNA barcoding

To read more about this research visit: www.ibol.org

To read more about barcoding, visit http://dna-barcoding.blogspot.ca/

Saving the honeybees

The Challenge

Agricultural production has been threatened due to a significant decline in honeybees, which pollinate about 75% of major global crops.

One of the largest causes of global honeybee population decline is the Varroa mite, a parasite that weakens honeybees and carries infection. The effect of this parasite can be minimized though hygienic behavior, which is a genetic trait that allows a bee colony to eliminate infected bees and prevent the spread of mites.

Identifying genetic traits that improve pest resistance in honeybees could address the issue of colony collapse disorder, a serious problem threatening the health of honeybees and the economic stability of commercial beekeeping and pollination operations worldwide.

The current process of selecting and breeding for honey bee stocks expressing hygienic behavior has its concerns: high labor costs associated with surveying and testing; screening currently has to be done late in the season after producers have spent a lot of time and money; the process involves killing several hundred bees per colony; the test is resource intensive so only a few beekeepers in Ontario can use it; non-hygienic honey bees can invade the colony, putting the others at risk.

The use of Varroa-resistant honey bees is ideal since the need for chemical-based treatments becomes unnecessary. There is a need to develop a selection process that is inexpensive and high-throughput with great precision and accuracy that allows beekeepers to better assess the hygienic capacity of colonies earlier in the beekeeping season.

Genomics solution

Dr. Amro Zayed\’s research is aimed at understanding and identifying genetic mutations that are associated with hygienic behaviour in honey bees, to lessen the impact of this devastating parasite on the industry.

By selectively breeding bees for improved hygienic behavior, we can increase their natural resistance to Varroa mites. And by improving colony hygiene, beekeepers can avoid chemical treatments, which can result in residue being left behind in the honey and wax, and lead to chemical-resistant pathogens.

Successes

This project will generate significant economic benefits to beekeepers and farmers in Ontario and Canada, including more effective breeding practices, cost savings in testing and bee loss, and upstream screening to cull non-hygienic colonies earlier in the season, and allowing a greater number of beekeepers to use the technology.

Autism: Genomes to outcomes

Autism is a developmental disorder that appears in the first three years of life, and affects the brain\’s normal development of social and communication skills.

The Challenge

  • Autism is one of the world’s most urgent public health challenges
  • Around one in 120 newborns is likely to have autism spectrum disorder (ASD), making it more common than type 1 diabetes, childhood cancer and cystic fibroses combined
  • The cost of treating autism is some $35 billion annually worldwide
  • Genes are the most likely culprit in causing autism, whether directly or indirectly, in upwards of 80-90% of individuals with ASD

The Research Solution

  • Drs. Stephen Scherer, Peter Szatmari and their team at The Hospital for Sick Children are using a $9.9 million LSARP award to help discover and characterize all of the genes involved in autism
  • This ground-breaking work will mark Canada’s contribution to an ambitious international initiative that aims to sequence and analyze the genomes of 10,000 people with autism spectrum disorder.
  • This work will help to facilitate early diagnoses, better medical management and individualize approaches to ASD treatment
  • By discovering all the autism rick genes, studies of environmental influences in ASD will be possible

Successes 

  • Numerous disease susceptibility genes have already been discovered and other genetic factors underlying autism have been defined
  • Recently, Dr. Scherer and his team discovered that a number of autism cases are linked to a gene found on the X chromosome, helping to explain why boys are four times more likely than girls to develop ASD
  • Current thinking is that there is over 100 different genes involved in autism, with 15% of those identified to date
  • The hope is that this information will help the development of drugs to treat autism

For more information on autism, visit: www.autismspeaks.ca

 

Finding the cause of rare diseases

The Challenge

Genetic diseases, while often rare, have, in aggregate, an enormous impact on the well-being of Canadian families, affecting the lives of approximately 500,000 children. The majority of genes causing these conditions are still unknown. These parents go through cycles of treatment and cost the health care system an inordinate amount of money considering the percentage of people affected. There is often no cure or any therapeutic treatment because the causes are unknown.

Genomics solution

Dr. Kym Boycott and collaborators used DNA sequencing to determine the causes of rare diseases that were put forward to the consortium by physicians across the country who deal with patients. The determination of the gene causing the diseases will then lead to a screening test for those particular disorders and also potential therapy options should the gene be identified in a well-known cellular pathway that drugs may have been designed for.

77 disorders were identified and four novel therapies were determined from this work. On a broader scale it showed the utility of these new genomic technologies to the clinical and to providing personalized care. While the economic modelling has not been done, the ability to know what gene causes a particular disorder and whether there is any therapy, will reduce the repeat visits to the clinic for the patients. In terms of quality of life, it is clearly of great benefit to the patients to get this information.

More information