In the 21st century we have an amazing amount of knowledge at our fingertips. This includes the human genome sequence – (most of) the 3,381,944,086 letters of DNA code for a human, known as the human genome sequence. It’s publicly available and you can look it up or download it if you have a computer with internet. Maybe some of us in the developed world are even starting to take it for granted.

The downloadable sequence is just a reference – each one of us has our own unique variation of this standard. Many of us now have reason to find out the sequence of one of our own genes, for example to see if we have inherited a higher than average risk of cancer, or if we carry a gene for a genetic disease. It’s even possible to get your own whole, unique, genome sequenced (at a cost).

In the 1980s the human genome sequence was a dream. Using the technologies available at the time we’d still be sequencing by hand. The Human Genome Project led to a lot of automated sequencing methods being developed – and they’re still being improved, which is still bringing the cost of DNA sequencing down.

This huge project was undertaken by many laboratories across the world. It was intended to be, and has been, a resource for improving health care. It’s not the only sequenced genome. Simpler organisms like viruses and yeasts, which have much smaller genomes, were sequenced before the human genome, and as time goes on we’re getting genome sequences for more and more living things.

So how was the human genome sequenced? There are a range of basic techniques and tools that allow DNA to be manipulated and  read. I’ve put together a Prezi which gives a visual overview of these tools.

Prezi: Tools for DNA discovery and innovation

DNA tools

To see this Prezi with more detailed explanations click on the link above.

DNA can be thought of as a long string of “letters” (nucleotide molecules) strung together. This makes up the code of life and it’s translated into a different language that can make any of the huge variety of proteins, like collagen, haemoglobin, insulin or botox. DNA can be cut, rearranged and joined back together. This makes it very versatile – it can be manipulated. It can be cut up and pasted into different organisms and the host organism will treat it like its own DNA – because the code of life is universal.

Another useful feature of the DNA molecule is that it’s made of two strands which pair together and each one can be made anew from its partner. Thus we can make new DNA in the test tube. One DNA strand can also find its partner so we can find or pick up a whole piece of DNA if we have a  just a small section of its partner.

So these tools for DNA analysis can also be used for our own purposes – for example. to make proteins such as human insulin in massive amounts. You can even make a gene from scratch if you know the code of the protein you want to make. But you’ll still need a live organism to process it into protein for you. Amazing! Diabetics used to rely on pig and cattle insulin, but the human version is better for us!

Cross posted from Fireside Science at SciFund Challenge

Further reading:

https://chromosomesandcancer.com/2013/06/18/the-human-genome-project-and-cancer/

https://chromosomesandcancer.com/2013/07/07/the-last-frontier-of-the-human-genome-sequence-repetitive-dna/

http://www.genome.gov/12011238

The Wellcome Trust’s Sanger Centre has a lot of information, videos and interactive tools that help explain DNA analysis and how the Human Genome was broken down into sections and sequenced. http://www.sanger.ac.uk/about/engagement/yourgenome.html

The WordPress.com stats helper monkeys prepared a 2014 annual report for this blog.

Here’s an excerpt:

A San Francisco cable car holds 60 people. This blog was viewed about 2,000 times in 2014. If it were a cable car, it would take about 33 trips to carry that many people.

Click here to see the complete report.

On the 9th of December there was a large oil spill in the Sundarbans of Bangladesh. Most of the 350,000 litres of furnace oil in an oil tanker spilt into the water. Check out these images from the BBC.

The Sundarbans in Bangladesh is the world’s largest contiguous tidal mangrove forest. The mangrove ecosystem is ecologically valuable, filtering contaminants out of the water. Mangroves are already threatened around the world. The Sundarbans is noted for its exceptional biodiversity but the oil spill is threatening many unique species including the Bengal tiger and the Ganges river dolphin. And mangroves are particularly sensitive to oil spills.

 

There’s also a huge human cost. The locals are not in the lucky position of having a government with money and technology to help clean up the mess. They’re scooping the oil out of the water with their bare hands. This oil is toxic and cancerous. Its components cause severe (poor prognosis) leukaemia. Children are exposing themselves. They need our help.

I’ve found a bit of news coverage online, but little from Australia’s government sponsored news broadcasters. There’s nothing from SBS (our overseas-focussed broadcaster), and only the one story from our ABC. This environmental disaster affects us not only because of the damage to a UNESCO World Heritage Site and the threat to wildlife, but also because the water in the Sundarbans is everyone’s water – it reaches your country in a manner of days. If the media won’t cover the story you can help play a crucial role. Pester the news media. Spread the story on social media.

Here are some tips on how to do this:

From Water Defense:

“Share information about the oil spill on your social media page to keep it top of mind. For the latest information check on Twitter @Sundarbans_SOS for regular updates and remember to use the hashtag #SundarbansOilSpill.”

From the River Dolphin blog:

“If this post bothers you at all, then I suggest you 1) contact major forms of news media (see post one for how to if you are in the US) and work HARD to get them to cover this story (US still not covering for the most part). 2) Write to the leaders of your country and ask them to pressure the government of Bangladesh to change this clean up solution IMMEDIATELY.  3) SHARE (don’t like… only sharing moves this story along) this post, and help us get the word out.”

An international response team including oil spill experts has now been sent to the Sundarbans in response to a request to the UN from the government of Bangladesh.

There’s an indiegogo campaign to raise money to get extra help to the Sundarbans – the not-for-profit Water Defense organisation wants to send a team to help clean the water. Why donate if there’s a UN team? Besides the obvious statement that a faster cleanup is better, there’s some controversy about using chemical dispersants to clean up oil spills. These dispersants end up in the water. The Water Defense team has a specially developed water cleaning foam that soaks the oil out of the water.

 

Follow Jennifer Lewis’s River Dolphin blog. Jennifer is the Director of the Tropical Dolphin Research Foundation. She reports on the human impact of the oil spill.

http://theriverdolphin.blogspot.com.au/

http://theriverdolphin.blogspot.com.au/2014/12/side-track-off-dolphins-for-one-post.html

http://theriverdolphin.blogspot.com.au/2014/12/ecological-disasterto-say-least.html

http://theriverdolphin.blogspot.com.au/2014/12/assessing-damage.html

 

More information:

http://news.nationalgeographic.com/news/2014/12/141216-sundarbans-oil-spill-bangladesh-tigers-dolphins-conservation/

http://news.sciencemag.org/asiapacific/2014/12/officials-scramble-respond-bangladesh-oil-spill

http://www.theguardian.com/environment/2014/dec/11/bangladesh-oil-spill-threatens-rare-dolphins

http://thinkprogress.org/climate/2014/12/24/3606793/experts-to-help-children-clean-mangrove-oil-spill/

http://whc.unesco.org/en/news/1209

http://en.wikipedia.org/wiki/List_of_oil_spills

 

 

 

 

This is a post from Francis Collins, the Director of the National Institutes of Health, and a well-known geneticist. It explains how genome sequencing can help people with a rare and unexplained genetic disease. I think he explains it clearly, what do you think? Is there anything that’s too technical for the layperson?

NIH Director's Blog

Hanners FamilyCaption: Whole genome sequencing revealed that sisters Addison and Trinity Hanners, ages 7 and 10, shown here with their mother Hanna, have a rare syndrome caused by a mutation in the MAGEL2 gene.
Credit: Courtesy of the Hanners family

At the time that we completed a draft of the 3 billion letters of the human genome about a decade ago, it would have cost about $100 million to sequence a second human genome. Today, thanks to advances in DNA sequencing technology, it will soon be possible to sequence your genome or mine for  $1,000 or less. All of this progress has made genome sequencing a far more realistic clinical option to consider for people, especially children, who suffer from baffling disorders that can’t be precisely diagnosed by other medical tests.

While researchers are still in the process of evaluating genome sequencing for routine clinical use, and data analysis continues to…

View original post 831 more words

As we’ve seen in previous posts, cancer is caused by some sort of error in the DNA of the cancer. Human DNA comes in 46 long strings called chromosomes and it sometimes breaks, but luckily the break is usually repaired. However, sometimes the repair process gets it wrong – for example two DNA ends are joined together that aren’t meant to be together.

This post is about a fairly recent discovery called chromothripsis. I’m going to describe it in terms of language, because after all, DNA is a language, and I think it will help picture what’s going on.

Anagrams are made by rearranging all the letters of a phrase or word to make another phrase or word, and it’s best if the new has a similar meaning to the old. Some examples are:

astronomer —-> moon starer
the meaning of life —-> the fine game of nil.

The rule for “perfect” anagrams is that all the letters are re-used in the new sentence.

Setting up printing originally involved arranging individual letters in a particular order on a plate. If the letters were dropped it wouldn’t be easy to get the letters back in the right order. If you had to put them back together in a hurry they’d be jumbled up and you wouldn’t get a meaningful anagram. In fact you’d probably have some missing letters left on the floor in a corner somewhere. Ok it’s starting to get complicated, but something similar can happen to DNA!

A printer inspecting a large form of type on a cylinder press. Each of the islands of text represents a single page, the darker blocks are images. The whole bed of type is printed on a single sheet of paper, which is then folded and cut to form many individual pages of a book.

At the beginning of 2011 Joshua Stephens and his colleagues published a paper that got a lot of cancer biologists excited. They noticed that the DNA of some cancers was very messed up. They even said that they’d found this in 10% of the cancers where they looked for it. Not only that, but they thought this had happened all at once by shattering of the chromosomes and rejoining of the broken pieces in a random and totally incorrect order.

Scientists love to make complicated words out of Greek roots. The Stephens paper called this process, this shattering and stitching back together of the chromosomes, “chromothripsis“. (An aside: The chromo- in chromothripsis is short for chromosome, or coloured thing. The authors say that thripsis means shattering into pieces.)

I had a couple of nice examples of chromothripsis acute myeloid leukaemia, but as someone who’s interested in chromosomes I wanted to talk about the chromosomes that were made by this whole chromothripsis process. There was no word for these new chromosomes so I came up with the term “anachromosome“. I like it because it has connotations of “new”, “remade”, and my favourite, “anagrams”. Although the anagram rule says all the letters have to be reused, there are apparently imperfect” anagrams which can leave out some letters to make the anagram work. This is more like an anachromosome. Inevitably lots of bits of chromosome don’t make it into the anachromosome and so are lost. Such wholesale shuffling and loss of large sections of DNA will probably kill the cell in most cases, but just occasionally it will produce a cell that can outgrow its neighbours – and turn cancerous.

This shows how the chromosome shatters and rejoins in a random order. Note that the two ends of the chromosome and the centromere (represented by a circle) are preserved. These are essential features of a functioning linear chromosome. From MacKinnon and Campbell 2013. Cancer Genetics 206:238-251.

This shows how the chromosome shatters and rejoins in a random order. Note that the two ends of the chromosome and the centromere (represented by a circle) are preserved. These are essential features of a functioning linear chromosome. From MacKinnon and Campbell 2013. Cancer Genetics 206:238-251.

References:

MacKinnon RN and Campbell LJ 2013. Chromothripsis under the microscope: a cytogenetic perspective of two cases of AML with catastrophic chromosome rearrangement. Cancer Genetics 206:238-251

Stephens PJ et al. 2011. Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development. Cell 144:27-40

In the summer of 2012-13 my daughter Katherine and her friends got together to make a short film during their holidays while they waited for their University offers.

Nearly two years later here it is.

 

 

sadako and golden cranesadako and golden bigsadako and golden boat

Paper Thin is based on the true story of Sadako Sasaki, who tried to fold 1,000 paper cranes to beat her leukaemia. This is an amazing short film directed by Elizabeth Duong with beautiful original music by Daniel Hernandez and Elle Graham. Don’t just take my word for it. Don’t just watch it. Don’t just like it.

Share Paper Thin to help make leukaemia HISTORY.

 

A generous, dedicated group of people have been working hard to create the story of  Sadako Sasaki in film to support our leukaemia research project.

Sadako survived the Hiroshima bombing in 1945. Radiation can kill quickly by causing radiation sickness, or slowly by causing cancer. Like many other children who survived the bomb, Sadako developed leukaemia ten years later when she was 12.

paper thin - liz's coming shot

The Director Elizabeth Duong and the Paper Thin Productions team is poweful both visually and emotionally. Daniel Hernandez and Elle Graham’s music can stand on its own.

So why Paper Thin? The story ties in with our research into leukaemia, and we’re aiming to raise awareness and support for the research.

This is crowdsourcing with a difference. Researchers worldwide are looking to alternative sources of funding as grant funding gets more and more competitive. Missing out on grant funding is not a short term problem. One very real problem is that skilled Scientists have to leave research.  That means the projects they’re working on stop and discoveries they were after will never happen. The expertise  they’ve build up won’t be used.

The most risky projects are the ones that make the biggest difference, the game-changing discoveries. But granting bodies don’t like risky projects. They like giving money to the big labs – this means more of the same.

Crowdsourcing is gaining in popularity – the people decide for themselves what research projects their donations will help.  In the case if Paper Thin there’s no middle-man crowdsourcing platform (they take a commission).

Another big difference is the product – this is a leukaemia story in film and music.

So because the Paper Thin Productions team’s given their time freely you can be sure 100% of your donation will go to the research.

THANK-YOU TO ALL INVOLVED

The credits do better justice than I could to acknowledge the people who helped. Special thanks also to Jenny Going from the Essendon Symphony Orchestra for allowing us to use their time to rehearse and record the music, and also to Shauna Hurley, Bridget Bible, Richard Prentice, Barabara Cytowicz, Leslea Johnson, Amber Atkinson and Kayanne Allan from St Vincent’s Hospital who helped with the logistics of how to do this from the Hospital’s perspective.

 

Carl Sagan was an astronomer and academic, best known for popularising astronomy. He hosted and co-produced the original hugely popular series Cosmos: A Personal Voyage.  Its sequel Cosmos: A Spacetime Odyssey was released this year. Even though I’m a biologist at heart I was fascinated by the original Cosmos.

Sagan was diagnosed with a myelodysplastic syndrome (MDS) and died at the age of 62, in 1996. In interviews near the end of his life he discussed myelodysplasia and said he was hopeful he’d been cured. He died at the Fred Hutchinson Cancer Research Center of pneumonia  after his third bone marrow transplant, a complication of this illness.

Most people with a diagnosis of MDS won’t have heard of it before. MDS is a group of bone marrow diseases. It’s at least as common as or more common than leukaemia but older people have a higher risk – perhaps one in 2,000 over the age of 60. A third of people with MDS will develop leukaemia. The 14th July, 2014, is the Leukaemia Foundation of Australia‘s second National MDS Day . One of the aims of MDS Day is to raise awareness of MDS.

Sagan’s illness was an opportunity to popularise MDS, but look how the cause of his death was described in these TV news reports.

In these news stories he was said to have died from a complication of “a rare blood disorder that led to cancer”, or “a blood disease”, “a bone marrow disease”, and even a” bone cancer” – the name of his disease was avoided.

Myelodysplasia literally means abnormal bone marrow cells. Blood cells are made in the bone marrow. In MDS the immature bone marow cells are abnormal and don’t mature properly. So the blood doesn’t have enough normal blood cells to do its job effectively. The blood is made of a number of different types of cells and the different types of MDS relate to the type of abnormal cell. MDS is often associated with a recognised chromosome abnormality, and identifying these chromosome abnormalities can help with diagnosis, treatment and prognosis. Therapy-related MDS is a specific type of MDS caused by treatment for a previous unrelated cancer and it usually has a poor outcome and very abnormal chromosomes.

MDS research has been neglected but has picked up recently. Some of the recent progress includes work by Carl Walkley and Louise Purton at St Vincent’s Institute in Melbourne, Australia.

MDS has had a history of name changes that seems to have made the meaning of its name less clear, except to medically trained people. This hasn’t helped improve public awareness of MDS. It was first named Di Guglielmo Syndrome in 1923 after its discoverer, then became refractory anaemia, then preleukaemic anaemia, preleukaemic acute human leukaemia, preleukaemia, and finally in 1976 the French-American-British Co-Operative Group of haematologists named it myelodysplastic syndromes. This recognised that it’s a group of related diseases and that not all cases will go on to develop into leukaemia.

Pathologist Ed Uthman, thinks Sagan’s Disease would be a better name for myelodysplastic syndromes – both as a tribute to Carl Sagan and a name that would mean more to most people than myelodysplastic syndromes.  Maybe he has something. Plenty of syndromes and diseases are named after people who studied them. Down Syndrome would have to be the best known example. Have you heard of amyotrophic lateral sclerosis? Motor neurone disease? Lou Gehrig’s disease? The first name is probably a nice technical description of the disease, but I’m guessing you’re more likely to  have an idea of what the disease is from one of the last two names, because they’re used in popular media and are connected in the public eye with famous sufferers – Stephen Hawking and Lou Gehrig. (Ed Uthman also think’s Lou Gehrig’s Disease should be “Hawking’s Disease”.)

I’ll let Carl Sagan have the last words on popular (mis)understanding of science (extract from Wikiquote).

We live in a society absolutely dependent on science and technology and yet have cleverly arranged things so that almost no one understands science and technology. That’s a clear prescription for disaster.

Every kid starts out as a natural-born scientist, and then we beat it out of them. A few trickle through the system with their wonder and enthusiasm for science intact.

(Cross-posted to Fireside Science at SciFund Challenge.)

I was privileged to speak at the Aspiring Women in Science conference in Brisbane, Australia last month. I think this is a fantastic initiative, which gives senior school girls an insight into working in various fields of Science (including Engineering and Medical specialties). Girls from years 10, 11 and 12 from all over Queensland were invited (mostly aged 15-17). Why girls? I attended a few of the talks myself and it reinforced my own view that there are experiences and conditions specific to women in Science. In talks on Science-as-a-career, information and advice from a woman’s perspective wouldn’t normally come up. It’s only fair to be as informed as possible when making a life choice. Both research and non-research careers were featured in the conference program.

We heard a lot of inspirational stories from Scientists in many different fields. Professor Ian Frazer – inventor of the Human Papilloma Virus vaccine Gardasil – was the keynote speaker. He spoke of his exciting adventures of discovery, from his childhood in Scotland to fulfilling his dream of building the Translational Research Institute in Brisbane. His dream will allow local scientific discoveries to be developed to commercialisation in Australia, instead of being sold to overseas companies. The virus (HPV) is a major cause of female cancer deaths in developing countries, and Prof Frazer is still battling to spread this message.

In the other sessions many women spoke of their work, of what excites and challenges all Scientists, and the challenges that women in Science in face because they’re women. Although we like to think that parents have equal roles nowadays,  a woman in research will likely have to decide whether she puts her children in childcare from a young age or give up research. Grandparents and other extended family are often not around to help because research fields are so specialised that researchers are likely to live far from their home town. These are stories that are familiar to me and were reinforced as I spoke to and listened to other women.

Several researchers, including Prof Frazer, spoke of the frustration of grant writing, the pressure of finding research funds, and the difficulty of sustaining a research career through short-term employment cycles. But more than one researcher also mentioned a published research study showing that a female name on an application for a (US) University Science position means the applicant is less likely to win the job, and the starting salary will probably be lower. Women also compete for grants, publication, promotion and leadership roles. And they drop out faster than men.

I don’t want to sound too negative, but students should be informed when they’re planning their future. I also believe things are slowly improving and if we keep on challenging the system it will keep on getting better. Being aware of the problem is part of working for a solution.

I can speak for scientific research and the thrill of discovery – if it excites you and you’re willing to give it a go – then go for it. Determination is part of the secret of success. I’m inspired by Jim Carrey’s lesson from his father: “You can fail at what you don’t want, so you might as well take a chance on doing what you love.”

But I do think that if you’re taking a risk it will be a bolder and better one if you have a safety net – such as family support, or a professional qualification as a backup plan.

I can’t pass up the opportunity to present these words from one inspirational woman about another, Maya Angelou (nothing to do with Science).

The Aspiring Women in Science conference was co-ordinated by Ela Martin and St Aidan’s Anglican Girls’ School in Brisbane. Part of the reason I was invited to speak is my history as a past student. I admire the school for making this conference and the school’s facilities and resources available to ALL girls in Queensland. Queensland’s a big place and some girls travelled a long way to make it. So, to Ela Martin and St Aidan’s, to Queensland University who supported the conference, and to all the Scientists who gave their time, a big thank-you for your initiative. I hope this idea has wings – per volar sunata.

 

Mitosis has to be one of the more beautiful things in nature. It’s a choreographed dance of the chromosomes. It’s so small that we can’t see it without a microscope, but it goes on in our bodies billions of times a day.

DNA is a very long molecule made up of the genetic alphabet (which has four letters: A, C, G, T). A gene is made of a certain sequence of DNA letters (or bases) and spells out an instruction for a step in the complex workings of our bodies (such as the structure of insulin). The genes are strung together along the chromosome, and each cell has a set of chromosomes. For our bodies to grow, these cells need to make copies of themselves. The problem of how to distribute the copied chromosomes evenly to the two “daughter cells” is handled very elegantly.

 

Chromosomes arrested at mitosis and stained with Giemsa (unbanded).

Human metaphase chromosomes stained with Giemsa (unbanded). The two halves of each chromosome are copies of each other.

 

Mitosis is the solution. Mitosis is broken up into a series of phases: interphase, prophase, metaphase, anaphase, telophase. You could break prophase up further by adding prometaphase: the part of prophase between the nuclear membrane breaking down and metaphase (where the chromosomes line up at the metaphase plate).

Now follow the captions under the pictures.

The interphase nucleus - the DNA from all the chromosomes intertwined with each other is represented by grey modelling clay. (Actually it seems that the chromosomes stay in relatively distinct domains - but under the microscope they appear as one entity.)

The interphase nucleus.   The DNA from all the chromosomes, intermingled with each other, is represented by grey modelling clay. (Actually it seems that the chromosomes stay in relatively distinct domains – but under the microscope they appear as one entity.) The DNA in the interphase nucleus copies itself as the cell grows.

 

The DNA in the nucleus starts to package and take shape as prophase chromosomes.

The DNA in the nucleus starts to coil up in a pre-determined order and take shape as prophase chromosomes.

 

The DNA folds up in a pre-determined order to make recognisable chromosomes. When the cell is ready to divide each chromosome has two chromatids or identical halves, joined at the centromere.

The DNA folds up further to make recognisable chromosomes. When the cell is ready to divide each chromosome has two chromatids or identical halves, joined at the centromere.

 

At metaphase the chromosomes meet in the middle of the cell at the metaphase plate. Then as the cell divides to become two daughter cells, the two halves of the centromere split and travel along the microtubules in opposite directions, pulling the two halves of the chromosome behind them.

Metaphase - the chromosomes line up in the centre of the cell at the metaphase plate. They are attached by their centromeres to microtubules which stretch across the cell.

Metaphase – the chromosomes line up in the centre of the cell at the metaphase plate. They are attached by their centromeres to microtubules which stretch across the cell.

 

At anaphase the two chromatids (half chromosomes) become the new chromosomes as they separate and move in opposite directions along the microtubules.

At anaphase the two chromatids (half chromosomes) become the new chromosomes as they separate and move in opposite directions along the microtubules.

 

The chromosomes start to unravel to form the two new daughter interphase nuclei. The cell membrane (the outer covering) pinches at the centre and the one cell finally becomes two (cytokinesis).

The chromosomes start to uncoil to form the two new daughter nuclei – telophase. The cell membrane (the outer covering) pinches at the centre (cytokinesis).

 

The cell membrane pinches at the centre (cytokinesis) so the cell finally becomes two cells.

Cytokinesis finishes and we have two new cells in interphase.

 

If a chemical that destroys the microtubules is added to a laboratory culture, the chromosomes are stopped at metaphase. Cytogeneticists (chromosome scientists) use this technique to get enough metaphase chromosomes for analysis. Chromosome banding helps us recognise the chromosomes and identify any changes when an abnormality is suspected. Of course, the cell is also full of other organelles that have to be shared between the new cells.

The modelling clay images above are from my claymation showing mitosis. Modelling clay is a great medium for demonstrating and thinking about how things work, move and change. For the claymation I used a phone camera resting face down on a glass coffee table over the models.

(Cross-posted from Fireside Science at SciFund Challenge.)