Grandma's Experiences Leave Epigenetic Mark on Your Genes | DiscoverMagazine.com
Your ancestors' lousy childhoods or excellent adventures might change your personality, bequeathing anxiety or resilience by altering the epigenetic expressions of genes in the brain.

According to the new insights of behavioral epigenetics, traumatic experiences in our past, or in our recent ancestors’ past, leave molecular scars adhering to our DNA. Jews whose great-grandparents were chased from their Russian shtetls; Chinese whose grandparents lived through the ravages of the Cultural Revolution; young immigrants from Africa whose parents survived massacres; adults of every ethnicity who grew up with alcoholic or abusive parents — all carry with them more than just memories.

Why can’t your friend “just get over” her upbringing by an angry, distant mother? Why can’t she “just snap out of it”? The reason may well be due to methyl groups that were added in childhood to genes in her brain, thereby handcuffing her mood to feelings of fear and despair. 

Like silt deposited on the cogs of a finely tuned machine after the seawater of a tsunami recedes, our experiences, and those of our forebears, are never gone, even if they have been forgotten. They become a part of us, a molecular residue holding fast to our genetic scaffolding. The DNA remains the same, but psychological and behavioral tendencies are inherited. You might have inherited not just your grandmother’s knobby knees, but also her predisposition toward depression caused by the neglect she suffered as a newborn.

Or not. If your grandmother was adopted by nurturing parents, you might be enjoying the boost she received thanks to their love and support. The mechanisms of behavioral epigenetics underlie not only deficits and weaknesses but strengths and resiliencies, too. And for those unlucky enough to descend from miserable or withholding grandparents, emerging drug treatments could reset not just mood, but the epigenetic changes themselves. Like grandmother’s vintage dress, you could wear it or have it altered. The genome has long been known as the blueprint of life, but the epigenome is life’s Etch A Sketch: Shake it hard enough, and you can wipe clean the family curse.

A new study suggests that Holocaust survivors’ descendants may have altered stress hormones because of epigenetics. (thanks tinglealley.)

Claims that these kinds of epigenetic changes – changes in the expression of our genes – are heritable remain somewhat contentious, but the studies keep coming and the evidence that this is possible really seems to be mounting. Two fascinating books on the subject are Tim Spector’s Identically Different: Why You Can Change Your Genes, based on his years of studying identical twins as a professor of genetic epidemiology, and Sharon Moalem’s Inheritance: How Our Genes Change Our Lives and Our Lives Change Our Genes, based on his work in rare diseases, neurogenetics, and biotechnology.

Some recent articles:


The secrets of cell development

Amazingly, all the cells in our body have exactly the same DNA and yet still manage to be completely different and carry out different jobs, from pumping our hearts to fighting off infections!

We have epigenetic marks to thank for this. Epigenetic marks (special molecules that attach at certain areas of the DNA) control how a DNA sequence is read and provide a mechanism for cell memory, without affecting the DNA sequence itself. These marks allow cells to interpret the uniform genetic information in different ways, by switching different genes on or off. The marks also help cells to remember which genes should be on and off and they can also pass this information onto other cells during cell division.

Without these epigenetic mechanisms cells would lose their identity, and to some extent that is what happens in diseases like cancer.

BBSRC-funded Professor Wolf Reik and Dr Fatima Santos, from the University Of Cambridge and The Babraham Institute, are studying stem cells, like the cells above, to find out more about epigenetic information: research which is providing us with new approaches to improve the potential of stem cells for regenerative medicine.

Copyright: Dr Fatima Santos

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Why Females Are Stripey

Each of us is made of a mixed-up jumble of cells. Most of you is you, but a few of your cells actually belong to your mom, stowaways that she left in your body.

But thanks to our sex chromosomes, it’s females who are the real mosaics. In this video from Veritasium, you’ll learn how biological females are like calico cats. Early in a female’s life, way back when her embryonic body was little more than a ball of cells just beginning to fold into basic patterns, a molecular coin was flipped inside each of her nuclei, and one of the two X chromosomes was silenced forever.

Why is this? Although our sex chromosomes are tiny compared to the other 44, they contain vital genes. But just like a genetic knockout can cause problems, so can too much of a gene product. Each cell in a female nucleus only expresses the genes on one of the two X chromosomes, muting the other so that the “dose” of X genes is pretty much the same between XY and XX individuals. 

Heads or tails, that epigenetic pattern persists for life, and although we can’t see them … women have “stripes”!

Bonus: Features the wonderful molecular animations of Drew Berry!

Biologists Induce Flatworms to Grow Heads and Brains of Other Species

Biologists at Tufts University have succeeded in inducing one species of flatworm to grow heads and brains characteristic of another species of flatworm without altering genomic sequence. The work reveals physiological circuits as a new kind of epigenetics - information existing outside of genomic sequence - that determines large-scale anatomy.  

The finding that head shape is not hard-wired by the genome but can be overridden by manipulating electrical synapses in the body suggests that differences in species could be determined in part by the activity of bioelectrical networks. The discovery could help improve understanding of birth defects and regeneration by revealing a new pathway for controlling complex pattern formation. It has long been known that neural networks exploit bioelectric synapses to store and re-write information in the brain.

The findings are detailed in the cover story of the November 2015 edition of the International Journal of Molecular Sciences, appearing online Nov. 24.

Tufts biologists induced one species of flatworm – G. dorotocephala, top left – to grow heads and brains characteristic of other species of flatworm, top row, without altering genomic sequence. Examples of the outcomes can be seen in the bottom row of the imageCenter for Regenerative and Developmental Biology, School of Arts and Sciences, Tufts University.

The effects of stress may filter right down to your brain's DNA.

An experiment showed that the amount of nurturing a mother rat provides its newborn baby plays a part in determining how that baby responds to stress later in life.

The pups of nurturing moms turned out less sensitive to stress because their brains developed more cortisol receptors, which stick to cortisol and dampen the stress response.

The pups of negligent moms had the opposite outcome, and so became more sensitive to stress throughout life. These are considered epigenetic changes, meaning that they effect which genes are expressed without directly changing the genetic code. And these changes can be reversed if the moms are swapped.

But there’s a surprising result. The epigenetic changes caused by one single mother rat were passed down to many generations of rats after her. In other words, the results of these actions were inheritable.

From the TED-Ed Lesson How stress affects your brain - Madhumita Murgia

Animation by Andrew Zimbelman

The Molecular and Cell Biology of Cancer - I

Cancer is a group of heterogeneous genetic diseases inherent in cells that proliferate in an unregulated manner. For a disease whose molecular characterisation began as recently as in the 70s, the span of these 4 decades have proven to be an aeon vis-a-vis breakthroughs in molecular oncology. Surprisingly, cancer holds an equally strong - almost ghoulish - fascination for the the general public, who probably think of it as the boogeyman of diseases; this is because, as real as the threat is, its scientific complexity continues to elude the masses. And yet it is everywhere, the poster child for hypochondria and morbidity alike: not only is it the go-to condition in popular literature and media, most of us can claim an acquaintance with someone affected. This apparent popularity may be justified, given that for roughly 14 million new cases diagnosed in 2012, 8.2 million existing patients died of cancer worldwide (1).

Through a series of articles, I will be writing about the science underlying carcinogenesis, about how genetic damage translates into molecular changes, which in turn shape the phenotypic hallmarks of the affected cells. Where applicable, this theoretical understanding will be complemented by the latest diagnostic and therapeutic applications.

So how does the process of tumour formation, called oncogenesis or tumourigenesis, begin? Essentially, the unrestricted growth and division that characterises cancerous cells can be attributed to endogenous (intrinsic) or exogenous (environmental) damage to our DNA, known as mutations. These mutations or genetic changes affect the production, structure and/or function of the molecules encoded by the affected genes. Therefore, oncogenesis has a genetic provenance, but at the cellular level, these changes manifest primarily as crosstalk between molecular components (usually *proteins*) of various signalling pathways within and between cells. *Figure 1 below comprehensively categorises the types of key proteins with a role to play in cancer cells*. The foremost goals of an altered signalling system are to overcome the Hayflick limit by repressing negative growth signals, and to favour survival over cell death (apoptosis); these two changes, along with other phenotypic alterations, are now known as the hallmarks of cancer (2). Collectively, these hallmarks confer a remarkable plasticity to cancer cells and will be discussed towards the end of this series.

Figure 1. The figure shows the chief protein classes involved in growth regulation, and thus cancer. Beginning from the membranous receptor proteins, signals are transduced to the nuclear machinery via downstream messenger proteins. The outcome of the nuclear gene expression further influences other cells by triggering their cell receptors, thus coming full circle.

The Genetics of Cancer

2015 began with an article in Science loosely citing “bad luck” as the major causative factor of cancer (3); the year ended with luck being trumped by exogenous (lifestyle and environmental) factors (4), more so than intrinsic damage. Regardless, the weakest links to take the first hit invariably remain the same: tumour suppressor genes (TSGs) and proto-oncogenes.  TSGs are anti-oncogenes that act as a dual line of defence to mutations, in that they are recessive (5). In other words, both alleles need to undergo two successive mutations for oncogenesis to proceed unhindered. This principle is now known as Knudson’s Two-Hit hypothesis, and was first observed by cancer geneticist Alfred Knudson in the retinoblastoma gene (RB); briefly, children suffering from retinoblastoma (Rb) were found to harbour two non-functional RB alleles that caused either familial or sporadic forms of the tumour. Children who had already inherited one defective allele from a parent required only one somatic mutation to the second functional allele for familial retinoblastoma to manifest. Genomes with completely wild-type RB loci were found to require two somatic mutations to both RB alleles for the sporadic form of retinoblastoma to develop. Knudson thus concluded that oncogenesis required both alleles of certain genes, such as RB in this case, to be knocked out (Figure 2) (6). It must be noted that the lines between genetic dominance and recessivity are blurred in the RB gene: a heterozygous RB locus possessing a wild-type and a mutant allele (denoted as RB+/-) is recessive in that the cell remains phenotypically unaffected. But in the larger picture, this very heterozygosity acts dominantly, because it pre-disposes the carrier to lose the second unaffected allele, and thus develop retinoblastoma. Let’s address how the remaining wild-type RB allele is knocked out instead of a random target in a small population of cells. 

Figure 2. The diagram illustrates the two modes in which mutations are acquired for retinoblastoma to develop.

In pre-cancerous cells, TSGs frequently undergo loss-of-function (LOF) in ways that circumvent the  requisite second mutational event, because the chances of that happening are exceedingly rare, in the order of 10^-12 per base per generation (10^-6/gen. times 2, for two alleles). During mitotic cell division, the chromatids from a mother cell duplicate their genome, forming two diploid chromosomes. Before the mother can further divide into two daughter cells, a chromatid arm from each chromosome may cross over and exchange segments of DNA in a process termed mitotic recombination. If the regions containing the tumour suppressor (ex. RB) alleles recombine, there is a 50% chance that one of the two daughter cells will lose the functional allele as well (Figure 3). This condition is predictably called Loss of Heterozygosity (LOH) (7). The rate at which mitotic recombination results in LOH lies in the order of 10^-2 to 10^-4 per cell division (8), which is oftener than the aforesaid second-mutation probability of 10^-12 per generation. However, rates specific to different TSGs are not the same.  

Figure 3. Mitotic recombination. The adjoining figure explains how mitotic recombination can result in crossover and the subsequent exchange of genetic information. To the far left are shown two homologous chromosomes that then duplicate their arms to form sister chromatids. The result of a crossover between 1 arm of each homolog is shown next, followed by the alternative fates of the daughter cells. The daughter cell to the far right ends up with homozygosity for the mutant alleles, shown in blue. 

Even if the chromatid arms escape recombination, things can go awry in the next step, that is, the segregation of the 2 pairs of sister chromatids into two cells. Each cell must receive one haploid copy of each chromosome; however, non-disjunction results in one daughter cell receiving both sister chromatids in addition to one chromatid of the other chromosome, and the other daughter cell receiving only one chromatid. One of the three chromatids (now chromosomes!) is later degraded down that cell lineage to maintain diploidy, and if it is the normal chromosome that’s degraded, this confers a homozygosity at the mutant locus for that line (Figure 4) (7).

Figure 4. Non-disjunction of sister chromatids. In the figure, the sister chromatids (green) are shown to segregate into one daughter cell, and if the normal chromatid (red) is subsequently discarded, the cell line becomes homozygous for the mutant locus. 

In accordance with the linked nature of the molecular chain of events, there’s always a ‘how’ or ‘why’ that proceeds a statement, and we might wonder why non-disjunction would occur in the first place. A not-too-onerous answer with molecular details will follow in a future article about cell cycles in cancerous cells, but to put things into perspective for the present, non-disjunction is a result of mis-segregation, i.e., an inability of the sister chromatids to separate, combined with the failure of the spindle assembly checkpoint to detect this error (7).This should demonstrate how cancer (or rather, onco-proteinic agents) is the perfect criminal, racing downstream via a parallel route and planning for all contingencies well in advance: not only do pre-cancerous cells possess a defective TSG allele, but they also facilitate the loss of the second allele by manipulating the expression of its upstream factors. In more optimistic terms, a single mutation or event is not enough to initiate and sustain cancer.

The third LOH mechanism is gene conversion, caused by the infidelity of the DNA polymerase (DNAP) that reads the DNA template during replication. Sometimes, the DNAP can promiscuously switch from its template strand to the strand of the homologous DNA sequence, thus reading the nucleotides of the wrong strand. If this misread region contains the mutated region, the new complementary strand will encode the inactive product (Figure 5) (7).

Figure 5. Gene conversion. The diagram illustrates the mechanism whereby DNA polymerase switches its choice of templates by temporarily shifting to the homologous chromosome (blue). Naturally, the unread segment in red will not be represented in the newly synthesised strand. 

Epigenetics is the final major mechanism in TSG suppression; in an event that is as rare as a second somatic mutation, the proximal region of TSGs can be hyper-methylated by DNA methyltransferase enzymes at the promoter regions rich in CpG dinucleotides. These sites then recruit histone deacetylase enzymes complexed with methyl-binding domain proteins (HDAC/MBD). Histones are multimeric proteins that wrap around DNA and modulate its structural condensation; if the DNA is tightly packaged around these histones, the resulting molecule is inaccessible to other proteinic factors. If on the other hand, specific  lysine residues on histone tails  have been acetylated by the HDAC-antagonist histone acetylase (HAT), the positive lysines are neutralised by the acetyl group. This reverses the electrostatic attraction between the negative DNA backbone and the histones, and the DNA loosens into an open, transcribable form, known as euchromatin.  Getting back to the point, HDACs strip the acetyl groups from lysine residues of the histones and revert them to their positively charged state. This disrupts the transcription factor (TF) binding sites formed by previously acetylated lysines, and TFs that promote expression of the downstream TSGs bind no more. Secondly, the now positive lysines are attracted to the negative DNA backbone and condense to form a closed chromatin structure, transforming from euchromatin to heterochromatin, which is not ideal for gene expression (Figure 6) (7). These mechanisms are referred to as transcriptional repression or gene silencing. The epigenetic ‘tags’, i.e. the methylated molecules, are exploited for diagnosis by methylation profiling of TSG promoters in tumour samples (9).

Figure 6. Euchromatin versus heterochromatin. The diagram compares the two alternative structures of DNA and its associated proteins. On the right, the histones wrapped round the DNA preceding the Transcriptional start site (TSS) are acetylated at lysine residues on their tail regions. 

Arguably the most important tumour suppressor, called the guardian of the genome, is the protein p53 (Figure 7). Ironically, its gene TP53 was initially classified as a proto-oncogene by the company that p53 was found to keep; this 53 kDa protein co-precipitated in complex with the large T antigen of simian virus 40 (SV40 AgT) in cancerous hamster fibroblasts (10), besides interacting with the anti-apoptotic Adenovirus E1B oncoprotein and with the E6 oncoprotein of Papillomavirus (7). It is now known that these viral proteins interact with p53 to inactive its tumour suppression functions. Notwithstanding these viral oncoproteins, TP53 is also frequently mutated gene in many types of cancers that results in its loss of function - different p53 mutations are found in more than 50% of all human cancers, with more than 45,000 mutations already curated (11). Moreover, the TP53 gene locus has been traced to a frequently deleted region on chromosome 17 in colorectal cancer (11). Therefore it is now incontrovertibly known as a tumour suppressor.

Figure 7. p53 bound to DNA substrate. The tetrameric structure of p53 is illustrated (yellow and pink) engulfing the DNA, visualised in green-blue. 

Both, pRb and p53 particularly crucial roles in cell cycle regulation, which explains why they are knocked out, inhibited, or targeted for degradation in cancer cell lines. Since this article has dealt with the mechanisms in which functional TSGs are lost, and taking into consideration that they are constantly involved in cancer cell metabolism, their manifold functions will be discussed over the course of future articles, as applicable.


  1. World Health Organisation [Internet] Cancer. [updated February 2015; cited 2016 January 14]. Available from: www.who.int/mediacentre/factsheets/fs297/en/
  2. Hanahan D, Weinberg R. Hallmarks of Cancer: The Next Generation. Cell. 2011; 144[5]:646–74.
  3. Tomasetti C, Vogelstein B. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015; 347[6217]: 78-81.
  4. Wu S, Powers S, Zhu W, Hannun Y. Substantial contribution of extrinsic risk factors to cancer development. Nature. nature; 2016;529[7584].
  5. Pierce B. Scitable [Internet]. Proto-Oncogene [updated 2005; cited 2016 January 14]. Available from: http://www.nature.com/scitable/definition/tumor-suppressor-gene-184
  6. Knudson AG. Two genetic hits (more or less) to cancer. Nature Reviews Cancer [Internet]. Nature Publishing Group; 2001;1(2):157–62. Available from: http://www.nature.com/nrc/journal/v1/n2/abs/nrc1101-157a.html
  7. Weinberg RA. The Biology of Cancer. New York: Garland Science, Taylor & Francis Group; 2014.
  8. California Institute of Technology [Internet] Mutations and Cancer lecture notes [cited 2016 January 17]. Accessed from: http://www.its.caltech.edu/~bi122/pdf/2015_Bi122_Lecture13.pdf
  9. Lehmann DR, Gallie BL. NCBI [Internet]. GeneReviews Retinoblastoma [updated 2015 November 19; cited 2016 January 14]. Accessed from: http://www.ncbi.nlm.nih.gov/books/NBK1452/
  10. Vogelstein B, Sur S, Prives C. Scitable [Internet]. p53 :The Most Frequently Altered Gene in Human Cancers; 2010. [cited 2016 January 15]. Available from: http://www.nature.com/scitable/topicpage/p53-the-most-frequently-altered-gene-in-14192717
  11. Leroy B, Anderson M, Soussi T. TP53 mutations in human cancer: database reassessment and prospects for the next decade. Human mutation [Internet]. 2014; Available from: http://onlinelibrary.wiley.com/doi/10.1002/humu.22552/pdf

Mom’s Diet Impacts Child’s DNA

A mother’s diet before conception can permanently affect how her child’s genes function, according to a study published in Nature Communications. The first such evidence of the effect in humans opens up the possibility that a mother’s diet before pregnancy could permanently affect many aspects of her children’s lifelong health.

Researchers from the MRC International Nutrition Group, based at the London School of Hygiene & Tropical Medicine and MRC Unit, The Gambia, utilized a unique, “experiment of nature,” in rural Gambia, where the population’s dependence on own grown foods and a markedly seasonal climate impose a large difference in people’s dietary patterns between rainy and dry seasons.

Read more: http://www.laboratoryequipment.com/news/2014/04/moms-diet-impacts-childs-dna

Biological Mechanism Passes On Long Term Epigenetic ‘Memories’

According to epigenetics — the study of inheritable changes in gene expression not directly coded in our DNA — our life experiences may be passed on to our children and our children’s children. Studies on survivors of traumatic events have suggested that exposure to stress may indeed have lasting effects on subsequent generations. But how exactly are these genetic “memories” passed on?

A new Tel Aviv University study pinpoints the precise mechanism that turns the inheritance of environmental influences “on” and “off.” The research, published last week in Cell and led by Dr. Oded Rechavi and his group from TAU’s Faculty of Life Sciences and Sagol School of Neuroscience, reveals the rules that dictate which epigenetic responses will be inherited, and for how long.

“Until now, it has been assumed that a passive dilution or decay governs the inheritance of epigenetic responses,” Dr. Rechavi said. “But we showed that there is an active process that regulates epigenetic inheritance down through generations.”

“A Tunable Mechanism Determines the Duration of the Transgenerational Small RNA Inheritance in C. elegans” by Leah Houri-Ze’evi, Yael Korem, Hila Sheftel, Lior Faigenbloom, Itai Antoine Toker, Yael Dagan, Lama Awad, Luba Degani, Uri Alon, and Oded Rechavi in Cell. Published online February 24 2016 doi:10.1016/j.cell.2016.02.057

How workers can become queens

A honey bee’s fate is decided at birth. The larvae develop to become a queen or a worker. If you’re born a queen, you get to rule the hive.

But other insects are more flexible.

For example, paper wasps and dinosaur ants are able to switch role from worker to queen at any point in their life - and new research uncovers the basis of this flexibility.

Researchers from the University of Bristol, the Babraham Institute and the Centre for Genomic Regulation analysed individual wasp and ant brains from queens and workers of both species to see whether caste differences could be explained by variations in how the genome is ‘read’ and regulated.

In the paper wasps as seen in the video above, the queen is identifiable by behaviours such as shaking the abdomen and aggression to exert dominance.

By looking at the genetic makeup of the insects, the researchers were able to determine what genetic influences were controlling behaviour.

They found very little difference between roles, which was surprising given that hundreds of genes are involved in determining the differences between queens and workers in the honeybee.

This suggests that there is no single master gene determining the role of these wasps and ants.

So you don’t have to be born a queen after all…

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Video: Solenn Patalano

DNA methylation landscape across development

DNA methylation for 5-methylcytosine-guanine (5mCG) and 5-methylcytosine-(A, T or C) (5mCH) is shown on separate scales across human development.

from the article “The landscape of DNA methylation amid a perfect storm of autism aetiologies”


brought to you by Graphic Services for Science

New Tool Pinpoints Genetic Sources Of Disease

Scientists have shown a connection between the “map” of genes in the genome and the “map” of reversible chemical changes to DNA, the epigenome.  Their finding could help disease trackers find patterns in those overlays that could offer clues to the causes of and possible treatments for complex genetic conditions.

DNA signature found in ice storm babies

The number of days an expectant mother was deprived of electricity during Quebec’s Ice Storm (1998) predicts the epigenetic profile of her child, a new study finds.

Scientists from the Douglas Mental Health University Institute and McGill University have detected a distinctive ‘signature’ in the DNA of children born in the aftermath of the massive Quebec ice storm. Five months after the event, researchers recruited women who had been pregnant during the disaster and assessed their degrees of hardship and distress in a study called Project Ice Storm.

Thirteen years later, the researchers found that DNA within the T cells - a type of immune system cell - of 36 children showed distinctive patterns in DNA methylation.

The researchers concluded for the first time that maternal hardship, predicted the degree of methylation of DNA in the T cells. The “epigenetic” signature plays a role in the way the genes express themselves. This study is also the first to show that it is the objective stress exposure (such as days without electricity) and not the degree of emotional distress in pregnant women that causes long lasting changes in the epigenome of their babies.

Mom’s in control – even before you’re born

Researchers have uncovered a way in which information contained in unfertilised eggs influences the development of the fetus and placenta during pregnancy. 

The research, performed in mice, indicates that even before conception a mother’s health may influence the health of her fetus. 

Epigenetic information is critical for determining which genes are turned on and off in our DNA. 

The researchers discovered that some epigenetic ‘marks’ laid down in eggs during their development in the ovaries and after fertilisation are passed onto the fetus and placenta. 

The findings suggest that mothers have the genetic tools to control the growth of their offspring during pregnancy by instructing placental development.

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Image credit: lunar caustic 


Researchers have developed a detailed picture of one of the complex molecular machines inside the nucleus of our cells.

A University of Wisconsin-Madison team of biochemists revealed the workings of a complex of five proteins called the spliceosome. This complex works together to edit out unneeded pieces of genetic code in RNA before it is used as a blueprint to produce proteins. 

To see how the spliceosome assembly works, they grew crystals of a part of it called U6. Among their findings is the complexity of the interactions between subunits of the complex, including one element that dives through a loop in another. 

Keep reading

Big Pic: A Fruit Fly Born In Outer Space

Something seems a little off here…

By  Francie Diep

This is a fruit fly, raised in space. Space was not directly what made it furred all over with white, but indirectly it was. The white stuff is fungus, and the fly grew it because after hatching and growing to adulthood in space, it didn’t fight off a fungal infection the way a healthy fly that had grown up on Earth would.

The image comes from the research of a team of biologists from several U.S. institutions. Observations of astronauts and studies done in human immune cells have shown that space weakens the immune system. This U.S. team wanted to learn more about what was happening at a cellular level. Their little spacefaring flies taught them that low gravity shuts off an important component of the fly immune system—one that has a human counterpart.  

Their findings gave them some starting ideas about why people also have compromised immunity after spending time in space, they wrote in a paper they published today in the journal PLOS ONE. One experiment they performed in hypergravity—created for the flies using a centrifuge in a lab on Earth—also suggested exposure to gravity could prevent the immune effects of space.

The team sent fruit fly eggs to space aboard the space shuttle Discovery. (Fun fact: These were the first flies to go into space in the name of immunology.) The eggs spent 12 days in space, during which time they hatched, crawled around a bit as larva, and became adult flies. Then they came back down to Earth, where biologists infected them with one of two things, either E. colibacteria or a fungus called Beauveria bassiana. (I survived space and all I got was a fungal infection.)

The space flies’ immune system fought off the E. coli, but not the Beauveria bassiana fungus. Meanwhile, similar control flies raised on Earth fought off both infections.

To figure out why the space flies had trouble with the fungus, the scientists analyzed all of the flies’ genes. Both the space flies and the Earth flies were born with the same genes, but exactly which of those genes turned on and went to work differed between them. In Earth flies, the genes associated with their immune systems kicked into high gear after they got infected with the fungus. Among other genes, Earth flies activated something called the Toll signaling pathway, which scientists have long known flies use to fight off fungi. Humans have Toll-like genes, too, and they also work in immunity.

The space flies reacted differently from their stay-at-home siblings. They turned on some immunity genes after encountering Beauveria bassiana, so it’s not like they were totally helpless. But they didn’t use all of the genes the Earth flies used, and they didn’t turn up their Toll pathway genes. In their paper, the biologists called their spacefaring flies “severely immunocompromised.”

Strangely, when the biologists raised flies in a centrifuge to simulate higher-than-Earth gravity, they were more likely to survive a fungal infection than normal Earth flies.

The science team offered some hypotheses about what could be happening that would alter what genes flies activate, depending on the gravity they’re exposed to. The hypotheses are testable, the team noted, although the team didn’t do that for this paper. The next step should be to send fruit flies to the International Space Station, the biologists wrote, where the little bugs can spend longer in space.

from Popsci

Controlling fear by modifying DNA

For many people, fear of flying or of spiders skittering across the lounge room floor is more than just a momentary increase in heart rate and a pair of sweaty palms.

It’s a hard-core phobia that can lead to crippling anxiety, but an international team of researchers, including neuroscientists from The University of Queensland’s Queensland Brain Institute (QBI), may have found a way to silence the gene that feeds this fear.

QBI senior research fellow Dr Timothy Bredy said the team had shed new light on the processes involved in loosening the grip of fear-related memories, particularly those implicated in conditions such as phobia and post-traumatic stress disorder.

Dr Bredy said they had discovered a novel mechanism of gene regulation associated with fear extinction, an inhibitory learning process thought to be critical for controlling fear when the response was no longer required.

“Rather than being static, the way genes function is incredibly dynamic and can be altered by our daily life experiences, with emotionally relevant events having a pronounced impact,” Dr Bredy said.

He said that by understanding the fundamental relationship between the way in which DNA functions without a change in the underlying sequence, future targets for therapeutic intervention in fear-related anxiety disorders could be developed.

“This may be achieved through the selective enhancement of memory for fear extinction by targeting genes that are subject to this novel mode of epigenetic regulation,” he said.

Mr Xiang Li, a PhD candidate and the study’s lead author, said fear extinction was a clear example of rapid behavioural adaptation, and that impairments in this process were critically involved in the development of fear-related anxiety disorders.

“What is most exciting is that we have revealed an epigenetic state that appears to be quite specific for fear extinction,” Mr Li said.

Dr Bredy said this was the first comprehensive analysis of how fear extinction was influenced by modifying DNA.

“It highlights the adaptive significance of experience-dependent changes in the chromatin landscape in the adult brain,” he said.

The collaborative research is being done by a team from QBI, the University of California, Irvine, and Harvard University.

The study was published this month in the Proceedings of the National Academy of Sciences of the United States of America.