Nobel Prize for chemistry of life

The 2009 chemistry Nobel Prize has been awarded to Venkatraman Ramakrishnan, Thomas Steitz and Ada Yonath.

The prize is awarded for the study of the structure and function of the ribosome - the cell's protein factory.

The ribosome translates genetic code into proteins - which are the building blocks of all living organisms.

It is also the main target of new antibiotics, which combat bacterial strains that have developed resistance to traditional antibiotic drugs.

These new drugs work by blocking the function of ribosomes in bacterial cells, preventing them from making the proteins they need to survive.

It's above and beyond my dreams and I am very thankful Ada Yonath

Their design has been made possible by research into the structure of the ribosome, because it has revealed key differences between bacterial and human ribosomes. Structures that are unique to bacteria can be targeted by drugs.

The announcement was made during a press conference at the Royal Swedish Academy of Sciences, during which the three winners were described as "warriors in the struggle of the rising tide of incurable bacterial infections".

Professor Ramakrishnan is based at the Medical Research Council's Molecular Biology Laboratories in Cambridge, UK.

Thomas Steitz is based at Yale University in the US, and Ada Yonath is from the Weizmann Institute in Rehovot, Israel.

The prize is to be shared equally between the three scientists, who all contributed to revealing the ribosome's huge and complex molecular structure in detail.

Professor David Garner, president of the Royal Society of Chemistry, described the three as "great scientists" and said their work was of "enormous significance".

'Molecular machine'

These scientists and their colleagues have helped build a 3D structure of the ribosome.

In doing so, they solved an important part of the the problem posed by Francis Crick and James Watson when they discovered the twisted double helix DNA structure - how does this code become a living thing?

Ultimately, when you look at any biological question it becomes a chemical problem Venkatraman Ramakrishnan

DNA is made available to the ribosome by "transcription" of genes into chunks of messenger RNA.

In the ribosome, these are read and translated into the various amino acid sequences that make up an organism's proteins.

By looking closely at its structure, scientists are able to study how this translation process works.

The work is based on a technique called x-ray crystallography - where molecules are removed from cells, purified and made into crystals that can be examined using x-rays.

Professor Ramakrishnan told BBC News that until the ribosome's atomic structure was determined, "we knew this was a large molecular machine that translated genetic code to make proteins, but we didn't know how it worked".

"We still don't know exactly how it works, but we have made a tremendous amount of progress as a direct result of knowing what it looks like.

"It's the difference between knowing that when you put gasoline in a car and press on a pedal, it goes. But if you know that the gasoline gets ignited and pushes down pistons and drives the wheels, that's a new level of understanding."

Work together

Addressing the Nobel press conference by telephone, Professor Yonath said that modern techniques were allowing scientists to look at the structures on the atomic scale - individual bond after individual bond.

New drugs targeting the ribosome will help fight resistant bacteria

This is the 101st chemistry Nobel to be awarded since 1901, and Professor Yonath is only the fourth woman to win. She joins an illustrious list of female chemists that includes Marie Curie, who also won the physics award.

During the press conference, Professor Yonath said: "It's above and beyond my dreams and I am very thankful."

President of the American Chemical Society Thomas Lane told the BBC that the award was "a wonderful example of leaders in their disciplines - people from around the world - working towards a common goal and being able to achieve it.

"It shows that as scientists we don't just sit in our dark labs, we come together and share our research."

Professor Ramakrishnan paid tribute to the many generations of talented researchers who he said had contributed to this entire field.

Some scientists have commented negatively that the research recognised by this year's chemistry Nobel has a biological focus.

But Professor Garner pointed out that "when you get down to looking at biology at the molecular level - understanding the fundamental processes of life - it's all chemistry".

Professor Ramakrishnan said: "Ultimately, when you look at any biological question it becomes a chemical problem, because bio is done by molecules and molecules use chemical laws."

He concluded: "It's often the way with science that people study fundamental problems, like the ribosome, and they lead to important medical applications in completely unpredictable ways.

"It's important to realise that support for basic science is the seed that allows the medical applications and technology to grow."

http://news.bbc.co.uk/1/hi/sci/tech/8294421.stm

Avoid Boring People - Avoid James Watson

"Avoid Boring People: And other lessons from a life in science, by James D. Watson"

I read this book, James Watson's autobiography, a few days ago. It was not very good, and it didn't particularly raise my respect for James Watson as a person or a scientist. The format of the book is the best thing about it - each chapter represents a stage in his life and at the end of each chapter a list of lessons and advice with a short explanation is given. Some of the advice is pretty good - if you plan to look through this book then just read the lessons that are relevant to you - no point in reading the whole thing...

James Watson's autobiography makes it blatantly clear that he did not struggle very hard to get where he is. He and his parents were middle class and he did not have any emotional or money trouble. He didn't have any family problems. He was intelligent and did well in school and met all the required grades to get into the colleges and universities and he never had any problems funding any of this. He never failed at anything he did and was never forced to take any unsavoury career routes or make any large compromises. Also he barely mentions anything about politics or the state of the nation and its affects on him.

He was always in education or in employment and he always had something to do and everyone around him supported him. The universities he worked for paid him well and funded all his research without debate (and this was before he discovered the structure of DNA). His choice of research was in the best field of its time (and now) - genetics. He gives advice concerning this along the lines of: Pick a research subject on the cutting edge of science. He says that picking a subject that has been studied extensively already or has little to contribute to humanity is not beneficial to an active scientist's career. I agree with him and can think of quite a few fields in science where funding should be cut off. But the point he was making is that if you plan to be a highly successful researcher, discover lots of new things and perhaps get recognition and/or a nobel prize, look at a subject where you explore uncharted territory that is beneficial to man (and could make you money).

As for his personal life, what can I say except that he never divulges anything about personal relationships with women or even his close friends (if he even had really close friends). He never mentions a single disagreement or serious debate he had with any person either personal or professional. He met with some of the most eminent scientists like Renato Dulbecco, Linus Pauling, Rosalind Franklin and a few others I've forgotten the names of, but he never mentions their personalities, quirks or how he interacted with them. Going back to his dealing with women... what women? He did not form any deep relationships with individuals and I think he remained a virgin till marriage or something - heck, he doesn't mention anything concerning emotions or attractions. He never had "women trouble" and he married one of his assistants because "when she wasn't there he missed her presence". He doesn't mention the courtship period or his anxieties or emotional strife (if any). Lazy & Boring.

As for discovering the structure of DNA he does something honorable - he mentions the highly significant amd neccessary contribution of Rosalind Franklin with her stunning X-Ray Crystallography photos and suggestions. He also mentions the point that other scientists rejected Linus Pauling's hurried publication of a paper in nature in 1953 which made them drop the idea of a triple helix and that other scientists' work in the field pointed them towards base pairing with the bases on the inside with the backbone forming a winding ladder on the outside. It was Franklin's photo that showed an X-like striations in the middle that made them sure that they were on the right path with base pairing on the inside. One irritation in this chapter of the book is that I learn next to nothing about Francis Crick. Yes he mentions him as his partner in this and his work being key to the discovery, but he doesn't mention anything about him as a person.

The genious behind the discovery of the DNA double helix structure was their using templates, initially paper cutouts, to fit together and see if the distances between the atoms in the molecules were acceptable. The fact that they used cutouts and arranged them in different ways is how they got to the answer. Sometimes visualisation is the key to discovery - imagine a large table of numerical values - as a table it might not look like there is a pattern in the data but once you plot it on a chart/graph and perhaps carry out a function on it, then you can discover a pattern and even model it. You would find it very hard to discover a trend just dealing with a list of numbers.

Nothing else is particularly interesting after that. He doesn't make any massive blunders, nor has he any serious problems. Yeh, he won a nobel prize which he was happy to get but a nobel comes quite a few years after the discovery and the scientist has moved on to a different challenge by then. He was happy to receive it but not extatic.

In summary, it's not a good book if you're looking to find out about his personality or personal life - he keeps his cards very close to his chest. He doesn't insult or mock anyone or bring up arguments or debates - either he is very cold emotionally or he wants to play it very safe. He doesn't describe himself, other people in character, quirks or appearance to make it interesting. The most controversial thing he ever did happened later on in his life a long time after the publication of this book when he said some things people saw as very racist (see here). If you do plan to look this book up there is no point in reading it fully - look at the photos and read the points at the end of each chapter instead. James Watson decided to call his autobiography "Avoid Boring People" and I agree - avoid James Watson.

I'm currently reading "Next" by Michael Crichton, a fiction book concerning genetics and its misuse. So far so good - I might write a post about this later. I might look at a Linus Pauling book next.

Key cancer spread gene found

Scientists have pinpointed a gene linked to more than half of all breast cancers.

The gene, NRG1 (neuregulin-1), is also thought to play a role in many bowel, prostate, ovarian and bladder tumours.

The University of Cambridge team said the breakthrough should provide "vital information" about how cancer spreads.

Experts agreed the finding, published in the journal Oncogene, could represent a very significant advance in the fight against cancer.

I believe NRG1 could be the most important tumour suppresser gene discovery in the last 20 years Dr Paul Edwards University of Cambridge

The Cambridge team showed that the gene - which helps to suppress the growth of cancer - is located on chromosome 8.

Cancerous cells are known often to miss part of that chromosome, and when the researchers analysed breast cancer samples they found that at least part of the key gene had often been lost.

Everybody is born with an intact NRG1 but it seems that in some cases it can become damaged - leaving the way open for cancer to thrive.

Lead researcher Dr Paul Edwards said: "I believe NRG1 could be the most important tumour suppresser gene discovery in the last 20 years as it gives us vital information about a new mechanism that causes breast cancer.

"We have got strong evidence that the gene is implicated in breast cancer but we have no reason to think it's not the same for other cancers, including prostate and colon cancer.

"Finding out what genes have been turned off in these cancers is enormous help in understanding what has gone wrong with their biology."

Arlene Wilkie, of the Breast Cancer Campaign, which part-funded the study, said: "Knowing the identity of this gene will lead to far more detailed studies of how it works and how it is involved in breast cancer development.

"This research is a major step forward in understanding the genetics of cancer and could open up a host of new strategies to improve diagnosis and treatment."

Lesley Walker, of the charity Cancer Research UK, which also funded the study, said more research was now needed to understand how the gene was silenced, and how exactly it influences the development of cancer.

She said: "It might then be possible to develop ways to bypass the gene or target treatments to the defect."

http://news.bbc.co.uk/1/hi/health/8290507.stm

Nobel prize for chromosome find

This year's Nobel prize for medicine goes to three US-based researchers who discovered how the body protects the chromosomes housing vital genetic code.

Elizabeth Blackburn, Carol Greider and Jack Szostak jointly share the award.

Their work revealed how the chromosomes can be copied and has helped further our understanding on human ageing, cancer and stem cells.

The answer lies at the ends of the chromosomes - the telomeres - and in an enzyme that forms them - telomerase.

The 46 chromosomes contain our genome written in the code of life - DNA.

When a cell is about to divide, the DNA molecules, housed on two strands, are copied.

But scientists had been baffled by an anomaly.

For one of the two DNA strands, a problem exists in that the very end of the strand cannot be copied.

Protecting the code of life

Therefore, the chromosomes should be shortened every time a cell divides - but in fact that is not usually the case.

If the telomeres did repeatedly shorten, cells would rapidly age.

The discoveries ... have added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies The Nobel Assembly

Conversely, if the telomere length is maintained, the cell would have eternal life, which could also be problematic. This happens in the case of cancer cells.

This year's prize winners solved the conundrum when they discovered how the telomere functions and found the enzyme that copies it.

Elizabeth Blackburn, of the University of California, San Francisco, and Jack Szostak, of Harvard Medical School, discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation.

Joined by Johns Hopkins University's Carol Greider, then a graduate student, Blackburn started to investigate how the teleomeres themselves were made and the pair went on to discover telomerase - the enzyme that enables DNA polymerases to copy the entire length of the chromosome without missing the very end portion.

Their research has led others to hunt for new ways to cure cancer.

It is hoped that cancer might be treated by eradicating telomerase. Several studies are under way in this area, including clinical trials evaluating vaccines directed against cells with elevated telomerase activity.

Some inherited diseases are now known to be caused by telomerase defects, including certain forms of anaemia in which there is insufficient cell divisions in the stem cells of the bone marrow.

The Nobel Assembly at Sweden's Karolinska Institute, which awarded the prize, said: "The discoveries... have added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies."

Carol Greider, now 48, said she was phoned in the early hours with the news that she had won.

She said: "It's really very thrilling, it's something you can't expect."

Elizabeth Blackburn, now 60, shared her excitement, saying: "Prizes are always a nice thing. It doesn't change the research per se, of course, but it's lovely to have the recognition and share it with Carol Greider and Jack Szostak."

Professor Roger Reddel of the Children's Medical Research Institute in Sydney, Australia, said: "The telomerase story is an outstanding illustration of the value of basic research."

Sir Leszek Borysiewicz, chief executive of the Medical Research Council, said: "The Medical Research Council extends its congratulations to Blackburn, Greider and Szostak on winning the 2009 Nobel Prize.

"Their research on chromosomes helped lay the foundations of future work on cancer, stem cells and even human ageing, research areas that continue to be of huge importance to the scientists MRC funds and to the many people who will ultimately benefit from the discoveries they make."

http://news.bbc.co.uk/1/hi/health/8290094.stm

Another Zend Framework Error - missing index.phtml

Something that isn't made especially clear is the way views and controllers work together. It hints at the issue in the ZF official tutorial here, but provides no clear message.

OK, the scenario - I've just created a new controller:

<?php

class UserController extends Zend_Controller_Action {

public function indexAction(){
echo "You are in the index of User";
}
?>

Running this in the browser by going to http://localhost/public/user will cause this error:

An error occurred

Application error

Exception information:

Message: script 'user/index.phtml' not found in path (C:\wamp\www\application\views\scripts\)

And it also outputs a stack trace and other stuff.

Evidently, there is a missing file issue here. Believe it or not, you need to create a phtml file corresponding to your controller and action! You have to go to the /applications/views/scripts/ directory and create a new folder called 'user' (or whatever you have called your controller), and you need to create a file in it called index.phtml and an additional phtml file for every action you create in all your controllers.

So lame.

Zend Framework View not found

I was messing about with a new installation of the Zend Framework on my system after reading through the basic tutorials on the web (the official ZF website tutorial is horrible) and I came across something that didn't work when using Views.

Here is the typical usage as shown in a tutorial on the IBM site (tut 2 [sign in required]):

<?php
//You should have require_once 'Zend/Loader.php'; in your bootstrap (index.php)

Zend::loadClass('Zend_Controller_Action');
Zend::loadClass('Zend_View');

class IndexController extends Zend_Controller_Action
{
public function indexAction()
{
$view = new Zend_View();
setScriptPath('views'); //the offending line
echo $view->render('indexIndexView.php');
}
}
?>

This is a typical controller class that makes a View object in order to render the HTML in the indexIndxView.php file to your browser. What should happen is that the contents of indexIndexView.php are displayed on your webpage. What actually happens is you get this error:

An error occurred

Application error

Exception information:

Message: script 'indexIndexView.php' not found in path (views\)

And then it outputs the stack trace and other stuff.

Evidently, this is a path problem - it doesn't know where to look for the files. Believe it or not, Zend didn't make their scripts auto-discover the location of the views folder! The thing is, the people who write the software and these tutorials should really mention these errors and how to get past them because it's things like this that put people off learning frameworks in the first place because the simplest things don't even work. Trying to Google this error is next to useless as it's really difficult to find the solution.

The fix is actually really easy:

$view->setScriptPath(APPLICATION_PATH . '/views/');

The APPLICATION_PATH is a constant set in the bootstrap file that can be used to make sure your files gets found. Why do people negelect to mention such important things?

Anyway, seeing the inadequecy of needing to create a view object and set its script path in every controller method, I decided to just create an instance of the view object in the bootstrap (index.php):

Zend_Loader::loadClass('Zend_View');
$view = new Zend_View();
$view->setScriptPath(APPLICATION_PATH . '/views/');

Then in every controller method I need to render a view in I just write this code (without the silly file naming OC):

global $view;
echo $view->render('indexIndexView.php');

Kohana PHP framework - some tips

Recently, I've been working with the Kohana PHP Framework and there are a few hurdles I've come across and gotten past - here are a few tips.

Making your own Controller

The default gateway controller with a fresh install of Kohana is 'welcome'. This means that URIs are written a bit like this:

http://localhost/kohana/welcome/index

But it's not ideal to have 'welcome' in the URI all the time. So, if you want to choose a custom name like 'site', you need to make your own controller...

1. Copy the welcome controller (welcome.php) in /kohana/applications/controllers/ and paste into the same folder.
2. Rename the file to site.php
3. Open the site.php file and change the class declaration to 'class Site_Controller extends Template_Controller'
   
4. Now, go to /kohana/system/config/ and copy the file called routes.php to /kohana/application/config/ .
5. Open up the file and edit like so: $config['_default'] = 'site';
   

That should do it. Your site will now build its URIs and route through the 'site' controller by default. You should make urls like so:

<?php html::anchor('site/index', 'Home Page'); ?>

Making your own default template

Simply go to /kohana/system/views/kohana/ and copy the template.php file to /kohana/application/views/kohana/. Edit the file as you wish. But, make sure your controller has this line pointing to it: public $template = 'kohana/template';

Making your CSS and Javascript work (get found)

So you make your XHTML template file and are ready to test everything - you stick your CSS in a .css file and your Javascript into a .js file and your images into an 'images' folder and put them in the root (/kohana/). You go to the page through the URI, e.g. http://localhost/kohana/site/index

Huh? What's this? Your CSS, Javascript and image files were not found!

Turns out you need to change the location of your files and add some PHP to your template.

1. make a folder in root (/kohana/) called 'media'.
   
2. make 3 folders called images, css and js inside your media folder and move your images, css and javascript files into their respective folders
3. Edit your css and js files to point to the right path for the images, e.g: background-image: url(/kohana/media/simages/bg.png); (make sure the first / is there otherwise it won't work
4. Now edit your template file to include this bit of code in the head section (I called my css file and js file css.css and js.js (imaginative huh?)):
   

<?php echo html::stylesheet(array('media/css/css'), array('screen')) .
html::script(array('media/js/js'), FALSE); ?>

Now this will put the typical XHTML tags into your page to include outside css and js files:

<link rel="stylesheet" type="text/css" href="/kohana/media/css/css.css" media="screen" />

<script type="text/javascript" src="/kohana/media/js/js.js">
In 1935, one of the founders of modern genetics, JBS Haldane, studied a group of men with the blood disease haemophilia. He speculated that there would be about 150 new mutations in each of us. 
Others have since looked at DNA in chimpanzees to try to produce general estimates for humans. 
However, next generation sequencing technology has enabled the scientists to produce a far more direct and reliable estimate. 
They looked at thousands of genes in the Y chromosomes of two Chinese men. They knew the men were distantly related, having shared a common ancestor who was born in 1805. 
By looking at the number of differences between the two men, and the size of the human genome, they were able to come up with an estimate of between 100 and 200 new mutations per person. 
Impressively, it seems that Haldane was right all along. 
Unimaginable
One of the scientists, Dr Yali Xue from the Wellcome Trust Sanger Institute in Cambridgeshire, said: "The amount of data we generated would have been unimaginable just a few years ago. 
"And finding this tiny number of mutations was more difficult than finding an ant's egg in an emperor's rice store." 
New mutations can occasionally lead to severe diseases like cancer. It is hoped that the findings may lead to new ways to reduce mutations and provide insights into human evolution. 
Joseph Nadeau, from the Case Western Reserve University in the US, who was not involved in this study said: "New mutations are the source of inherited variation, some of which can lead to disease and dysfunction, and some of which determine the nature and pace of evolutionary change. 
"These are exciting times," he added. 
"We are finally obtaining good reliable estimates of genetic features that are urgently needed to understand who we are genetically."
http://news.bbc.co.uk/1/hi/sci/tech/8227442.stm