Marked by pain

Chronic pain can be marked in the DNA

The work was published in the open-access journal PlosOne. To model pain, scientists injured nerves in the tight of laboratory mice through surgery. The purpose of the study? To understand if the lesion remains in the DNA of cells as a mark.

The research showed that epigenetic marks can be found in the DNA of cells from brains of mice suffering from chronic pain. Epigenetics comprises the chemical marks in the DNA and associated proteins that are the product of signals and stimuli arising from different sources. In the same way as each cell is characterized by its genes (genetics), it is now clear that cells are also characterized by the chemical modifications in those genes (epigenetics). Even if epigenetics cannot change the sequence of genes in the DNA molecule, it can control the way genes are "read". In this experiment, peripheral nerve injury led to epigenetic alterations in the brains of the mice, at the level of DNA, as if to remind the animals of the lesion suffered 6 months before.

credits: Ana Costa
A new system for quantifying pain can
originate from the new observations.  

 It is not clear yet which consequences originate from the epigenetic marks in specific regions of the brain. To better understand the mechanism observed, scientists induced symptom relief, to some extent, by means of exposing the mice to modified cages (a procedure somehow similar to a series of physiotherapy sessions). The changes in the symptoms were associated with changes in the epigenetic marks of the DNA molecule in the brain cells. Scientists learnt that the marks in the DNA could be related by the levels of pain.

In the future, will this information be useful to those patients suffering from chronic pain, regardless of its cause? The authors of this study are optimistic about the future and believe that one day it will be possible to treat pain if the epigenetic marks in the DNA are modulated by clinicians. And even if the treatment of pain is far from reality, these new observations can start by serving another purpose: that of quantifying pain. Currently, assessing pain in complex due to subject to subject variability. However, establishing a more objective method of quantification could be beneficial for the correct diagnosis and treatment of various pathologies. This new study can be the basis for a new, epigenetics-based, quantification method for pain.

Epigenetics of cancer

Cancer signatures extend to epigenetic marks. Credits: Ana Costa

Cancer's new signatures:

Epigenetic modifications are conserved among various metastases in the same person.

Today’s EpiPost focuses on a new discovery concerning prostate cancer and its metastases. The report published in Science Translational Medicine (23rd January 2013 ) highlights the need for personalized medicine by showing that the patterns of epigenetic modifications vary considerably between lethal prostatic tumours from different men but are maintained within the tumour and metastases in the same person.

Epigenetics is the layer of genomic regulation that is not due to the sequence of As, Ts, Cs and Gs in the DNA molecule, but instead relies on chemical marks found in nuclear DNA and its associated proteins. These epigenetic marks that sit on DNA, namely the methylation mark, are very relevant from the point of view of physiology, as they may shape to the way cells responds to stimulus, both from outside, and from inside the cell itself. In recent years, scientists have observed that tumours display their own patterns of DNA methylation and those differ from the ones found in the “normal” cells of the same person. This observation led to the question: can DNA methylation be used as a diagnostic biomarker for cancer?

So far, the general belief that DNA methylation patterns varied too much in each patient's widespread cancers procrastinated the development of diagnostic strategies or even therapies. Now, with the help of new biochemical and computational technologies, scientists from the Johns Hopkins University, in Baltimore, USA, made two seminal observations that may change this view: first, that the DNA methylation patterns were considerably altered between tumours from different individuals; and second, that tumours and metastases from the same individual had identical DNA methylation patterns. For this analysis, the samples were obtained from autopsies of men who had died of metastatic prostate cancer. Both samples from the various metastases, as well as samples from normal tissues were collected for genomic comparisons.

The results led the scientists to conclude that each cancer evolves to acquire its own characteristic signature of DNA modifications, and that this epigenetic signature is maintained at sites of metastases. This observation has a close parallel to what is known about genetic alterations of tumours, which are also stable within each individual. As with genetic alterations that contribute to the onset and dissemination of cancer, epigenetic changes are also to be taken into account when investigating the events leading to cancer progression.

The new data revealed that new biomarkers of aggressive cancers lie in the epigenetic landscapes of each patient’s cancer cells. Scientists believe that this knowledge will help in the early identification of these forms of cancer and may possibly contribute to the development of therapeutic strategies directed at each person’s specific cancer epigenetic signatures. 

Hard Drives or DNA?

Hard drives made of DNA:

not only genes can be stored in DNA molecules

Not only genes can be stored as DNA. Credits: Ana Costa

Ready, set, go: DNA is now much closer to become the new platform for information storage. Scientists have attempted to develop the technique for a while, and a recent report (commented here ) has proven that it is possible to store data in DNA as if it was a hard drive, meaning than not only small pieces of information can be stored, but that the advances are compatible with numerous big files. More importantly, there is a serious potential for this to become the ultimate tool in data storage: it is very stable over time and is becoming cheaper every day.

To test their hypothesis, scientists at the European Bioinformatics Institute(EBI) in Hinxton, UK, and at the Agilent Technologies in California, USA, had to decide what information to store in the DNA. They wanted to store files with different formats – pictures, texts, sounds - to prove the flexibility of the new platform. The choices were eclectic and included: a collection of Shakespeare’s sonnets, Marthin Luther King’s memorable “I have a dream” speech, Watson and Crick’s 1953 original paper on the molecular structure of DNA, and a photo of the EBI, located south of Cambridge.

Using an algorithm, bytes were converted into the 4-letter code found in the DNA molecule. Long molecules of DNA encoding particular pieces of information were then synthesized, a procedure that has greatly developed in the recent years, overcoming the high costs and errors that characterized this technique in the past. The synthesized DNA was stored lyophilized and shipped across the Atlantic at ambient temperature in common packaging. In this way, the authors wanted to prove that this is a very practical system that does not require any special handling or storage conditions. Upon arrival, the DNA was “read” so that the information could be decoded. The sequencing machines work fast nowadays and it didn’t take long until scientists were able to recite Shakespeare in the lab.

Are these promising results? Yes. Can we use DNA instead of hardware in the future? Maybe not. DNA will probably never become your first choice of storage material because you would need access to synthesizing and sequencing machines and those can only be found in well-equipped labs, not in one’s living room. However, if your lab produces high amounts of data and you are considering storing it for a long time but accessing it scarcely (or never) in the future, DNA may well serve your purposes

Right now scientists are busy discussing if DNA is the ultimate apocalypse-proof storage material that can survive fire, storms, earthquakes and all kinds of disasters in a much better way than would hard-drives. Of one thing at least we can be sure of: DNA was here much before hardware was, so it may well last longer too!!

The best kept secret

The best kept secret: 

How to trick normal cells into becoming neurons.

credits: Ana Costa.
A variety of different proteins characterizes each cell type.

A recent report (17th january, Cell) has presented evidence that cell types other than neurons, such as cells of the connective tissues, can be turned into neurons only by controlling the levels of one protein in those cells. 

So far, this “trick” is the simplest and more straightforward way ever reported to obtain neurons in the lab, as other previously employed methods involved the use of many compounds and were less efficient. The results are exciting, but the important step of replicating this work in animals is far from reality, at least for now. At the moment, scientists are trying to understand if they can achieve the same results in whole organisms (moving from in vivo to in vitro systems). Positive results would definitely have a great impact on the way we deal with neurodegenerative diseases (Parkinson’s, Alzheimer’s and others).

Strategies aiming at preserving damaged neurons or attempts to slow down the rate of neuron deterioration have not considerably improved the quality of life of those affected with neurodegeneration. Now, these results will prompt the scientists to explore a promising new route: the conversion of cells that lie nearby the damaged neurons into new neurons.

And in addition to the promising new therapeutics, one cannot avoid envisioning a scenario where even healthy individuals could profit from this technique: - Why not ask your doctor to boost your pool of neurons? You may consider getting just a couple more to help you pass the final exams; or you can go big and request a pile of fresh new ones to address the list of long-standing prize money-earning unsolved mathematical problems.

Machine2013

MACHINE 2013

From the brains of the bees

Of bees and…

credits: Ana Costa

From the brains of honeybees, we learned that epigenetics can control social behaviour and career changes.

EpiPost

Epigenetics…let’s get started.

The text below refers to laboratory results published back in 2011. However, those results are a good example of what epigenetics can mean to our lives. If, after reading the post, you’re more confused than before, don’t worry – even senior scientists working in this field for a long time can be surprised by the experimental results related with epigenetics!

I am writing about a paper published more than a year ago to start a new series called: EpiPosts. More to come soon – how can we resist this topic?!