The Next Generation

FOR A WEEK GENE RESEARCHER GENE RESEARCHER

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Diseases such as cystic fibrosis,

juvenile diabetes, and muscular

dystrophy come down to a roll of the

genetic dice and the only cure in sight involves

scientists WORKING AT THE EDGE OF POSSIBILITY.

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The Canadian Institutes of Health Research- Institute of Genetics (CIHR-IG) is committed to exciting and motivating the next generation of scientists through our Gene Researcher for a Week program. This hands-on experience in Canada’s top research labs is an investment in Canadian youth and science.

By supporting and encouraging young scientists, CIHR-IG paves the way for Canadian research to be part of the global genomics conversation. Genetic research is dramatically changing the medical

Welcomelandscape and it’s possible that in the future, any one of our participants will solve the most complex medical riddles of our time. It was, after all, Canadians Frederick Banting and Charles Best who saved the lives of millions of diabetics with their discovery of insulin. You can be part of the next step: a cure for that disease or the dozens of others that create hardship for patients and their families.

The Gene Researcher for a Week program opens doors for students who want to be part of a growing network of researchers who will have an enormous influence on the future of medicine. Welcome to the opportunity of a lifetime.

“ What has been so important to me is knowing that I could make a difference in the lives of patients with a particular defect. Scientists can completely change patients’ lives by the contribution they make to a diagnosis and ongoing treatment.”

DIANE WILSON COX University of Alberta, Department of Medical Genetics, discoverer of the gene responsible for Wilson disease

CIHR Institute of GeneticsLetter from

CIHR Institute of Genetics McGill University 3649 Promenade Sir William Osler Room 279 Montreal, QC H3G 0B1

August 16, 2016

Re: Gene Researcher for a Week

Training the next generation of genetic researchers is at the core of our mission. CIHR-IG is pleased to have the opportunity to continue the Gene Researcher for a Week program, which in the past was organized by the Canadian Gene Cure Foundation. Since its inception in 2003 over 450 students from all over Canada have been introduced to hands-on genetic research, and many of these students have continued with a focus on genetics in their undergraduate and graduate studies.

We are deeply grateful to the scientists who host these students and provide such valuable experiences for them, and we applaud the students who take part for their interest and dedication.

Sincerely yours,

Paul Lasko PhD Scientific Director, CIHR Institute of Genetics

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Genetics laboratories are gateways into a world most people never see — DNA, the molecule that makes us human and distinct from each other.

Genetic research involves two different ways of studying DNA. Cytogenetic laboratories look at chromosomes from cell samples taken from a person’s blood, skin, or other tissue. Lab technicians grow the cells, which are later placed on slides and stained so they are easier to see under a microscope. Molecular genetic laboratories, on the other hand, look at one particular gene’s DNA. A molecular geneticist examines the DNA sequence of a gene looking for errors — not easy when a single gene has thousands, or even millions, of letters of code.

Labs will vary from institution to institution but Gene Researchers for a Week can expect to be part of a team. Anywhere from a handful to dozens of people work side-by-side — technicians, research assistants, and principal investigators all have a role to play in advancing research projects.

Some labs focus on searching for mutations that cause cancers. Others concentrate on genes associated with disorders that lead to heart disease, or on genes implicated in neurological disorders, such as autism and ADHD. Still others might look at specific defective genes, like the one that causes Wilson disease, a genetic disease in which people accumulate too much copper in their tissues. Some laboratories also use their genetic expertise in forensics, solving legal problems through science.

“ One of the best things about being scientists is

that we do things that have never been done before — we open knowledge fields that did not exist before. We’re at the edge of current knowledge. Even

if our names are not attached

to a breakthrough, it will be

useful for humanity for a

long time and that’s a gratifying aspect of the profession.” ERIC BOUCHARD Division of Genetics, Université de Sherbrooke

GENET IC HERITAGEAustrian monk Gregor Mendel spent eight years in the 1860s growing 28,000 pea plants to examine seven of their traits. What would happen, he wondered, if he cross-pollinated a tall plant with a short one, or a green plant with a yellow one?

When these hybrids produced offspring, Mendel noted which plants had which characteristics, such as short/tall, green/yellow, or wrinkled/smooth peas. His work proved that individual traits were physically passed from generation to generation and that some traits were more dominant than others.

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The humble fruit fly couple produces three generations and three million flies in a month — ideal for studying inheritance. In 1904,

scientist Thomas Hunt Morgan noted that fruit flies passed on physical traits just as Mendel’s pea plants did, except for one thing: gender made a difference. For example, in flies, the female passes

on eye colour. Morgan thought that chromosomes inside the nucleus of the cell held the secret to why this happened.

Picture yourself holding what looks like a high-tech turkey baster over a flask: that’s called pipetting cells and one of the jobs often entrusted to a Gene Researcher for a Week. Once the cells are in the proper environment, they’re placed in an incubator to grow so the chromosomes can be looked at under the microscope. Sometimes students have the opportunity to grow cells from their own tissues samples.

To read DNA, a genetic sequence has to be extracted from cells first. Scientists use a range of equipment and techniques to make an extracted sequence visible. One of the most common pieces of technology in a lab is the PCR (polymerase chain reaction) machine. Once teased from a cell, a DNA fragment is amplified by a thermal cycler — it’s like a DNA photocopier churning out lots of copies so a genetic code can be read more easily.

Another technique is a yeast assay, which makes DNA visible only after the encoded protein is created. The interactions of the protein with certain other molecules can then be studied. Under special test conditions, the yeast cells will not grow if the DNA is mutated and encodes a defective protein. This can help scientists understand how a disease works and to imagine ways to manipulate it — in other words, to find a cure.

The chief requirements of being Gene Researcher for a Week are familiar ones to participating students: be engaged and ask questions. Curiosity is expected. Laboratories will vary in the work assigned to students, but each lab strives to give a full overview of how research is conducted.

GENET IC HERITAGE

“ I became a researcher because I’m curious, I like trying it figure out how things work. It’s

like working on a puzzle — looking for all the little pieces that fit.” MATTHEW BAN Robarts Research Institute, The University of Western Ontario

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The scientists appreciate the Gene Researcher for a Week program as much as the students. The students bring a fresh perspective to the research setting and researchers get to share the daily life of a working laboratory.

Most labs provide reading materials to acquaint students with research protocols and background information on the studies carried out in a particular institution. While students will find the most up-to-date equipment in labs — instruments that sequence a human’s entire genome and microarrays that allow fine-scale comparisons between individual genomes — the classic techniques of cytogenetics are probably familiar to anyone who has participated in high school life science classes.

The weeklong program, however, is a serious crash course in the DNA molecule. It will help to learn a bit more about DNA before arriving at the lab — what does it do, where does it live, and how do scientists manipulate the molecule to tell us more about the human condition? To work in a lab often means waiting for data, and you’ll have snatches of time for reading more about the work being conducted by the researchers and their roles in the wider gene research community.

At the end of the week, Gene Researchers for a Week will leave with a snapshot of what a career in genetics has to offer from those actually doing genetic research. And after meeting research assistants, graduate students, and principal investigators, students will also come to understand that many paths can lead to science.

Rosalind Franklin, a chemist, took the first clear photo of DNA in 1952. She used a technique called x-ray crystallography — it sprays molecules with x-rays, which bend and spread in a certain pattern when they hit the molecules. Called “Photo 51,” the image was an important clue to deciphering the structure of DNA.

At about the same time, microbiologist Barbara McClintock was the first to theorize that genes could move on and between chromosomes. McClintock studied the colour patterns of maize kernels.

“ What I really like about being a scientist is the

independence and the ability to pursue questions of interest and to do that with a lot of young, really bright, committed and enthusiastic people around.”

GEORGINA MCINTYRE University of Alberta, Department of Medical Genetics

GENET IC HERITAGE

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• Are genetic laboratories safe?

Every laboratory has safety procedures in place. Most labs do not use radioactive material and only researchers and technicians work with blood samples. The key is to follow safety protocols.

• What should I wear?

Comfortable clothes and close-toed shoes. Clothing that drapes or is loose can get in the way especially when working with delicate instruments.

• Can I wear contact lenses?

No. Lab chemicals can get trapped between your eye and the lens. Wear your glasses.

• Will I have time to understand the material?

Researchers are there to answer questions. Students will have material to review and will be prompted with questions themselves to

make sure they understand the research procedures.

• Can I work with strands of my own DNA?

Some labs might have a project that includes looking at the student’s karyotype, some might not. If so, written permission is requested from a student.

• Am I expected to donate my DNA for a database?

No.

• What if I want to donate my DNA for a database?

To compare genes that are mutated with normal genes, researchers collect DNA from all kinds of people and populations. There is usually a collection process in place. Students can ask researchers how an institution gathers DNA for a database.

• Can I clone myself?

No, that’s not possible.

Francis Crick and James Watson used geometry to figure out that the cross-shape of the DNA molecule in Photo 51 was

actually part of a twisting ladder, which they called a double helix. In 1953, they built the first correct model of the DNA molecule, with cardboard. Along with Maurice Wilkins, they

were awarded the Nobel Prize in Physiology/Medicine in 1962 — interesting, considering Wilkins and Crick were physicists by

training, while Watson, a biologist, originally studied birds.

StudentFAQs

GENET IC HERITAGE

“Molecular biology is a term that seems very narrow, but there

are many different techniques and approaches

that we use to get at this overall

question of what in the DNA makes one person

different from everyone else.”

RICHARD WINTLE The Centre for Applied Genomics,

The Hospital for Sick Children

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DO

• know where to find safety and emergency equipment

• learn all lab procedures before working

• wear any safety accessories provided

• keep work area clean and tidy

• keep hair tied back if long

• wash hands before leaving the lab

• know location of emergency exits

• wear clothes that cover legs, torso, arms, and feet

• keep hands away from mouth, nose, and eyes

• keep coats, purses, and backpacks in designated areas

DON’T

• wear dangling jewellry

• chew gum

• wear loose clothing

• wear open-toed shoes or high heels

• work in the lab alone

• drink or eat in the lab

• wear synthetic fingernails

• attempt to catch a falling object

• directly touch any substance with your hands

• handle any containers that are too heavy for you

• sit on a lab bench

“ You get as much as you put into this program, so ask as many questions as

you can think of and don’t

be worried about looking

unintelligent because we

are all learning.”

Gene Researcher for a Week

ALUMNUS

All laboratories pose some hazard and everyone who works in one goes through a training process. Training and tests can take about two hours. Gene Researchers for a Week must follow the same safety procedures as researchers and technicians. Students will be taught a lab’s security set-up and given a checklist of what is allowed and what is not allowed. For example:

GENET IC HERITAGEIn early 2003, scientists from many countries, including the United Kingdom, United States, France, Germany, Japan, Canada, and China, published the results of a collaborative international effort, the Human Genome Project. Scientists found far fewer genes than they expected. Nematode worms have about 17,000 genes and humans have about 25,000. The exact number, however, is still uncertain. Scientists also discovered that proteins, which build tissues and regulate body functions, were more complex than anticipated.

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The number one piece of advice from student participants in the program was to learn more about genetic labs in general, and about their host lab in particular. Second, they advise that knowing some basic information about genetics research would have made their transition to Gene Researcher for a Week a bit easier. Third, when appropriate, take lots of photos.

Find out more about what kinds of equipment you’ll encounter. For example, the PCR machine:

• From the DNA Learning Centre, animated explanation:

http://www.youtube.com/watch?v=2KoLnIwoZKU

• In the lab:

http://www.youtube.com/watch?v=sGP56W0CSV8&feature=related

To find out beforehand the research your assigned lab does, ask the program coordinator for contact information. Some labs have websites. For example:

• The Centre for Applied Genomics at the Hospital for Sick Children in Toronto

http://www.tcag.ca/index.html

Ask your science teacher for basic reading. Some background information on genetics can be found at these websites:

• Map of the human genome:

http://www.ncbi.nlm.nih.gov/mapview/map_search.cgi?taxid=9606

• An online extended talking glossary (and pronunciation guide) explains some basic concepts:

http://www.genome.gov/glossary/index.cfm

• How we know what we know:

http://www.genome.gov/Students/

• Genome sequencing and assembly for non-scientists, from Dr. Richard Wintle at The Hospital for Sick Children:

http://occamstypewriter.org/irregulars/2010/12/11/genome-sequencing-shakespeare-style/

http://occamstypewriter.org/irregulars/2010/12/31/genome-assembly-a-primer-for-the-shakespeare-fan/

In 2010, genomics researcher Craig Venter and his team used yeast to create a genome from scratch. The yeast, Deinococcus radiodurans, can be exposed to high

levels of radiation, which blows its chromosomes apart; however, within a day it can reassemble its DNA into proper sequences. The team created pieces of DNA, injected

them into the yeast, which then assembled the human-made genome. Synthetic genomic research may eventually help solve environmental problems — by rewiring

the DNA in algae, for example, to make biofuels.

GENET IC HERITAGE

Advicefrom Alumni

“ Find your own voice and courage — if you haven’t found what work you love doing, keep looking.”

MICHAEL HAYDEN Killam Professor of Medical Genetics at the University of British Columbia, director of the Centre for Molecular Medicine and Therapeutics

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High school students today will likely be the people whose individual genetic codes are routinely included as part of any medical procedures in the future. Gene Researchers for a Week have the unique opportunity to share what it’s like to work in a genetic lab.

Most teachers are flexible — they want you to share the excitement of the week with the class. Work out ahead of time how much time you have for your presentation. If you took photographs, use them: people want to know what a PCR machine looks like, what exactly is pipetting, what do working scientists do, and what does a scientific lab looks like.

You might want to explain genetic vocabulary with classmates. While working in a lab you’ll become familiar with many terms. The talking glossary is a useful tool to use with a presentation.

Articles from the popular media can also help you make genetic research more easily understood.

• Time, Why Your Genes Aren’t Your Destiny:

http://www.time.com/time/magazine/article/0,9171,1952313,00.html

• The Globe and Mail, Researcher who carries gene for Huntington’s disease:

http://www.theglobeandmail.com/life/i-know-how-i-am-going-to-die/article787356/

• Scientific American, Genomics for the Rest of Us:

http://www.scientificamerican.com/article.cfm?id=personal-genome-sequencing

“ The cost of sequencing the first human genome was about $400 million. Today, the cost of sequencing one genome stands

at $9,500, and, within the next four or five years, we expect to reach the point where we can sequence an individual’s genome for $1,000 or less. This impressive decline in cost has fueled a rapid expansion in the medical applications of DNA sequencing and related technologies.”

FRANCIS COLLINS physician and geneticist who led the Human Genome Project to completion in 2003

SCHOOLS

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The Canadian Gene Cure Foundation (CGCF) is a registered Canadian charitable

organization. A group of dedicated visionaries and members of the Canadian Genetic

Diseases Network (CGDN) who strongly believe more funding is needed for medical

genetics research in Canada formed the foundation in 1999.

The Institute of Genetics (IG) is one of the 13 virtual institutes that make up the Canadian

Institutes of Health Research (CIHR). The IG community is made up of researchers,

scientists, community groups, and individuals from Canada and around the world who

are interested in knowing about the human and model genomes and gene interaction with

physical and social environments.

The IG supports research on all aspects of genetics, basic biochemistry and cell biology

related to health and disease. The IG in compilation with CIHR initiatives collaborates with

a wide range of federal and provincial funding organizations as well as non-governmental

and health charities.

The Foundation and IG joined forces to sustain a cooperative research community in the

field of human genetic disease, increasing the likelihood of successful discoveries of

cures and treatments for inherited diseases.

The Gene Researcher for a Week program was created to support this goal: fostering the

growth of genetic clinician-scientists by inspiring high school students in Canada. In the

years to come, these emerging scientists may be the ones who will make groundbreaking

discoveries, and translate these findings to improved patient treatment and care.

CIHR-Institute of Genetics also thanks the following: Matthew Ban (University of Western Ontario), Yohan Bossé (Université Laval), Carolyn Brown (University of British Columbia),

Kristi Baker (University of Alberta), Nafisa M. Jadavji (Carlton University), Michael Hoffman (University of Toronto), Richard Wintle (The Hospital for Sick Children)

CIHR—Institute of Genetics www.cihr-irsc.gc.ca/