my-genes-made-me-do-it

On the face of it the weirdness of quantum mechanics and biology would seem to have nothing to do with each other. Quantum mechanics deals with the subatomic world and biology with much larger things like cells. Any quantum effects in cells would be cancelled out by the multitude of noisy biological processes. But not so. Quantum biology refers to the many biological processes that involve the conversion of energy to usable chemical transformations and are quantum mechanical in nature.

Examples are photosynthesis, vision, magnetoreception in animals, DNA mutation, and the conversion of chemical energy into motion. Any process that involves the transfer of electrons and protons in chemical processes uses quantum mechanical effects. In photosynthesis it has been shown that the wave and particle conundrum occur simultaneously. The wave spreads uniformly to potential receptors, while the particle follows the path of least resistance through the field of potential created by the wave. This makes for a 95% efficiency in energy transfer.

Many important biological processes taking place in cells are driven and controlled by events that involve electronic degrees of freedom and, therefore, require a quantum mechanical description. An important example are enzymatically catalyzed, cellular biochemical reactions. Here, bond breaking and bond formation events are intimately tied to changes in the electronic degrees of freedom. For more quantum biology examples, click here.

Finally in neuroscience there is a debate as to whether the brain is a quantum computer -- that the microtubules within neurons have the capability to perform quantum computation . Stuart Hameroff  believes that the tubulin subunits which make up a microtubule are able to cooperatively interact in a quantum computational sense.

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CRISPR is causing a major upheaval in biomedical research.  It is cheap, quick and easy to use, and it has swept through labs around the world as a result.

What is CRISPR? - it is an abbreviation for ‘clustered regularly interspaced short palindromic repeats’. It was  initially found in bacteria as a resistance mechanism to foreign genetic material such as plasmids and phages.

CRISPRs are associated with cas genes that code for proteins related to CRISPRs —  Cas9 for instance  By delivering the Cas9 protein and appropriate guide RNAs into a cell, the organism's genome can be cut at any desired location. Researchers only need to order the RNA fragment; the other components can be bought off the shelf. Total cost: is as little as $30. This effectively democratises the technology so that anyone can use it.

Last year, bioengineer Daniel Anderson of the Massachusetts Institute of Technology in Cambridge and his colleagues used CRISPR in mice to correct a mutation associated with a human metabolic disease called tyrosinaemia. It was the first use of CRISPR to fix a disease-causing mutation in an adult animal — and an important step towards using the technology for gene therapy in humans.

What are the risks?

Many researchers are deeply worried that altering an entire population, or eliminating it altogether, could have drastic and unknown consequences for an ecosystem. They are also mindful that a guide RNA could mutate over time such that it targets a different part of the genome. This mutation could then race through the population, with unpredictable effects - the risk of the accidental release of an experimental gene-drive.

What is a gene-drive?

First let us look at how mutations are normally spread within  populations.

STD-1

With gene-drive the genetic change would spread rapidly throughout the population since at each mating the genetic change would occur in both parents.

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For further information, the source article is: Nature 522, 20–24 (04 June 2015)

 

Tao-to-MS2

If you have read the previous post The Tao of Intelligence then you can ignore this one. I am trying an experiment to see how much the title of a blog post can influence the traffic to the post. However the change of title is not a trivial one. How else could a ssRNA molecule of 3569 nucleotides result in the building of an elegant icosahedral virus particle (pictured above) and orchestrate a molecular dance of grace and poise utilising the twists and turns and foldings of its RNA genome?  All of this in the absence of a Designer — just by following its ‘path’ — the force of intelligence.

Pithovirus

Although this made headlines around the world, it is probably only of concern to amoebae and evolutionary virologists. But the researchers suggested that as the Earth's ice melts, this could trigger the return of other ancient viruses, with potential risks to human health. The scientific virological community responded by pointing out that this "stretched scientific rationality to the breaking point" (Curtis Suttle - University of British Columbia, Vancouver)

This is not to say that this virus does not have some interesting properties -- it is the largest virus at 1.5 micrometers long (the size of a small bacterium) -- one end appears to sealed with a cork (photo) -- the French researchers named it from the Greek word 'pithos' for the large container used by the ancient Greeks to store wine and food. It is unrelated to other giant viruses such as Mimivrus or Pandoravirus that have been isolated from amoeba. Pandoravirus has a large viral genome at 2.8 million base pairs compared to Pithovirus at 0.6 base pairs. Only 32% of the predicted Pithovirus proteins have homologs in protein databases (this number is 61% for Minivirus and 16% for Pandoravirus).

Pithovirus hints at the vast unimagined viral diversity that awaits our discovery.

For more, see article by Professor Vincent Racaniello

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The short answer to the question: -- YES.

Following on from the previous posting about Pandoraviruses, the virological world has become much more complex than we could have imagined -- a network of diverse genetic elements with different reproduction strategies and lifestyles -- the transpovirons, polintons, and virophages.

Virophages
Comparison of the genome architectures of the virophages, polintons, some viruses, and transpovirons. Homologous genes are marked by the same colors. (CLICK TO ENLARGE)

The rapid advances of genomics and the growth of sequence databases has led to the discovery of fundamentally novel types of genetic elements. The giant viruses, Mimiviruses that infect amoeba, possess their own parasites and communities of associated mobile genetic elements. The first virus infecting a giant virus, the Sputnik virophage, was shown to replicate within the mimivirus factories and partially inhibit the reproduction of the host Mimivirus. A second isolated virophage was named Mavirus and the third virophage genome was isolated from the Antarctic Organic Lake (hence OLV, Organic Lake Virophage). The virophages possess small isocahedral virions and genomes of 20 to 25 kilobase encoding 21 to 26 proteins.

Analysis of the Mavirus genome resulted in the unexpected discovery that this virophage shared 5 homologous genes with the large, self-replicating eukaryotic transposable elements called Maverick/Polintons. In addition to the virophages, the giant viruses host several other groups of mobile elements. These include self-splicing introns, inteins, putative bacterial-type transposons and the most recently discovered novel linear plasmids named transpovirons. In a recent paper published in the Virology Journal, the authors sought to decipher the evolutionary relationships between the three known virophages, the Maverick/Polintons, transpovirons and bona fide viruses.

Their conclusion was that the virophages and related genetic elements formed a vast network of evolutionary relationships with multiple connections between bona fide viruses and other classes of non-virion mobile genetic entities -- a genetic soup.

Gut-Bacteria
Microbes are everywhere and we are host to trillions -- many of them in our gut. These experiments illustrate how gut bacteria transplanted from mice that had received gastric bypass helped other mice lose weight too. Below is a summary of the research:

Obese people considering gastric bypass surgery to help trim their fat might one day have another option: swallowing a new supply of gut bacteria. A study in mice suggests that weight loss after bypass surgery is caused not by the operation itself, but at least in part by a change in the amounts of various species of microbes in the gut. A bypass operation separates off a small part of the stomach and connects that directly to the intestines. Recipients tend to feel less hungry, fill up more quickly and burn more calories at rest, and they often lose up to 75% of their excess fat. Counter-intuitively, this is thought to be caused by a change in metabolism, rather than by the reduced size of the stomach. Gut microbes are thought to be part of this picture. People who have had bypasses are known to experience changes in the selection of microbes in their guts. Fat people have been shown to host a different selection of gut bacteria from people who are obese, and transferring the gut bacteria of fat mice into thin ones can cause the thin mice to pack on extra weight. But no one knew whether the microbes in bypass patients changed because they got thin, or if the patients got thin because the microbes changed. To investigate, Lee Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston, and his colleagues gave about a dozen obese mice bypass surgery. As expected, the mice lost about 29% of their body weight, and kept it off despite a high-fat diet. New conditions in their bodies — such as a change in bile acids — allowed a different set of gut bacteria to thrive. The results are promising for obesity treatments, but there are still hurdles to overcome. “You can’t just take a pill of the right bacteria and have them stick around,” says Seeley. If the gut’s environmental conditions don’t change, then the original microbes come back, he says. Kaplan says that the next steps are to isolate the four bacteria types that the study found to be at play and introduce them into obese mice or people. Antibiotic treatments might help the new bacteria to stick. “I believe it’s possible,” says Kaplan.

For the original article: click here

circular-RNA
Circular RNAs can act like molecular 'sponges' binding to and blocking tiny gene modulators called microRNAs. These circular RNA molecules comprise "a hidden parallel universe" of unexplored RNAs that control gene expression. Typical RNA-sequencing methods did not detect this molecules unless they had a molecular 'tail'.

Erik Sontheimer, a molecular biologist at Northwestern University in Evanston, Illinois said: “It’s yet another terrific example of an important RNA that has flown under the radar,” you just wonder when these surprises are going to stop.” Previous accounts of circular RNAs in plants and animals were generally dismissed as genetic accidents or experimental artefacts. Nikolaus Rajewsky, the lead author of one of the studies and a systems biologist at the Max Delbrück Center for Molecular Medicine in Berlin focused on a circular behemoth, some 1,500 nucleotides around, that is expressed in the brains of mice and humans. They found that it contains about 70 binding sites for a microRNA that can block gene expression linked to cancer and Parkinson’s disease.

Circular RNAs could also be sponges for microRNA from outside the cell, notes Rajewsky. Some have possible binding sites for viral microRNAs, which can subvert immune responses. He hypothesizes that circular RNA could even interact with RNA-binding proteins. “They are so abundant, there are probably a multitude of functional roles.”

This discovery goes further to illustrate that life is such a rich tapestry of interconnecting elements that it truly challenges our ability to fathom its complexity.

Reference: Nature vol: 494, pg 415 (28 February, 2013)

Aubrey de Grey, a British researcher on aging, has drawn a roadmap of how we can defeat biological aging.

Normal metabolism leads to cell damage -- the goal of Gerontology is to prevent the damage before it happens. Geriatric medicine is about ameliorating the pathology of the damage.

cell-damage-1The focus of damage control is on the long-lived molecules. Also there is possible control of genes by the FOXO protein -- the activation of the latent ability of the cell for self-repair.

Cell-damage-2Using a mouse model some of the targets for damage control have been successful.

cell-damage-3

For more here is Aubrey ...

Aging is thought to be a natural and inevitable decline as our body wears out. But research carried on C. elegans, a small laboratory worm, by Cynthia Kenyon challenges this view. They found that mutations in the DAF-2 receptor for hormones dramatically altered the lifespan of these worms.

Ageing-1

This is thought to work by releasing FOXO which activates the latent capacity for the worms to live longer than they normally do -- by activating the cell's ability to repair itself.

Ageing-2

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Why did this system arise in evolution?

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Further studies in other species including mice has confirmed this overall pathway. This also explains the effects of restricted calories for the longevity in some humans.

How could we use this research? The search is on for some small molecule that could alter the activity of the DAF-2 receptor -- mimicking a mutation and activating the cell's repair mechanisms -- thereby delaying aging. For more, watch the TED Talk.

The human genome contains 3 billion letters but only about 3% codes for proteins -- the rest was tagged as 'junk'. Based on this concept Craig Venter and others set out to create the minimal functional genome with no junk and as reported in a previous blog The Synthetic Wheel of Life, he was able to replace a synthetic yeast genome into a cell devoid of a genome -- and it worked but still contained junk DNA.

Everything changed with ENCODE (Encyclopedia of DNA Elements) -- currently it has been shown up 80% of the DNA is functional and is used to control and modulate gene expression and to make all the different kinds of cells in our body. It is likely that the 80% will go to 100% and there will be no 'junk' DNA.

"Think of the human genome as a city. The basic layout, tallest buildings and most famous sights are visible from a distance. That’s where we got to in 2001. Now, we’ve zoomed in. We can see the players that make the city tick: the cleaners and security guards who maintain the buildings, the sewers and power lines connecting distant parts, the police and politicians who oversee the rest."  (from Discover Magazine)

There are many implications for ENCODE from redefining what is a 'gene' to providing clues as to how the genome works in three dimensions. It gives us a new way to look at diseases and conditions like cancer.