Cutting-Edge Reports

Cutting-Edge Reports

Epigenetics 101

20th February 2018

Epigenetics is the study of mechanisms which affect gene expression without changing the sequence of DNA. Many of these mechanisms are heritable across generations. Picturing Waddington’s Epigenetic landscape, in 2018 we would imagine it more like a seabed; containing different layers, with each contributing a part to the overall topology on the surface. We can picture each undersea peak as a stem cell state. From here a rock would follow a trajectory mapped by the surface topology, ending in a hollow (a differentiated state). The layers of information are diverse and many have only begun to be investigated. In this short introduction, we’ll deal with some current threads and interesting new discoveries in the field, focusing on three broad themes of epigenetics.

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BY DR MOYRA LAWRENCE

Epigenetics in disease and the promise of therapy

20th February 2018

Known epigenetic changes typically occur in normal development, regulating the normaldifferential expression and silencing of genes. However, certain epigenetic alterations have been implicated in disease. Specifically, a disruption in any of the epigenetics “systems”, DNA methylation, histone modifications, transcription factor binding, and RNA-associated silencing can cause abnormal gene silencing or expression leading to undesirable consequences such as cancer, mental disabilities such as Fragile X, Angelman’s, and Prader-Willi syndromes, as well as other diseases that result from chromosomal instability.

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Skin Organoids that grow hair!

10th January 2018

A team of scientist at Indiana University have succeeded in growing mouse skin organoids that grow hair. Like other types of organoids, these are grown in a 3-D gel matrix and receiptulate the different components of skin including hair follicles. This means that the mini-organs or skin organoids do grow hair in the dish!

In nature, the mammalian hair follicle appears during embryonic development and results from the coordinated interactions between two layers of the skin: the epidermis and dermis. In the reported study, the researchers have grown the follicles producing skin organoids from mouse pluripotent skin stem cells.

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Image credit JIYOON LEE AND KARL R. KOEHLER via EUREKALERT

Using ultrasound to localise engineered bacteria in a host organism

by Sarra Achouri

Bacetria can also be healthy for us

Our microbiome has many proven roles in mammalian – therefore human – health and disease, for example in immunity and central nervous system disorders.

Modern genetic engineering has allowed the design of microbial therapeutics and diagnostics as reported for the detection of cancer in urine, the treatment of colitis in the mouse, the use of synthetic microbes as drug delivery systems, the synchronisation of bacterial lysis cycles for in vivo delivery, or the long-term use of engineered bacteria in the mammalian gut as live diagnostics of inflammation.

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The Twelve Days of CRISPR

by Robin Floyd

On the first day of CRISPR my true love sent to me,

A tag with a GFP.

On the second day of CRISPR my true love sent to me,

Two cancer screens

And a tag with a GFP.

On the third day of CRISPR my true love sent to me,

Three T-cells

Two cancer screens

And a tag with a GFP.

On the fourth day of CRISPR my true love sent to me,

Four hornless cows

Three T-cells

Two cancer screens

And a tag with a GFP.

On the fifth day of CRISPR my true love sent to me,

Five dead Cas9s

Four hornless cows

Three T-cells

Two cancer screens

And a tag with a GFP.

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CRISPR: Background and Basics (Part 2)

by Robin Floyd

In Part 1, we established that the CRISPR/Cas system is a component of adaptive immunity in many types of bacteria which works by cutting DNA – usually belonging to invading viruses – at a position specified by an attached guide RNA molecule. Two scientists, Emmanuelle Charpentier and Jennifer Doudna, initially interested simply in understanding the workings of bacterial RNAs, first showed in a 2012 paper that the Cas9 enzyme could be “re-programmed” by attaching a synthetic RNA, which caused it to search for and cut any DNA with that same code. Though they demonstrated this only in test tubes and not in living cells at the time, the implications were clear. Working at around the same time but published in early 2013, Feng Zhang used a further-modified CRISPR/Cas9 system to make genomic edits in laboratory-cultured mouse and human cells – leading to a still-unresolved patent battle over which of these groups is the real “inventor” of this technology.

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CRISPR: Background and Basics (Part 1)

by Robin Floyd

CRISPR genome editing is one of the hottest topics in current science; we have already written about it several times on this blog, and it seems that hardly a week goes by without a new CRISPR-related story hitting the headlines. So this series of articles is intended as a reference for those who may be curious about the basics: what is meant by CRISPR, why are biologists so excited about it, and why does it have such a weird name which seemingly bears no relation to what it does?

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CA methylation and epigenetic memory

by Dr Moyra Lawrence

Epigenetics is the study of how information can be transmitted without altering DNA sequence.This can occur through changes in DNA methylation, histone modification or chromatin conformation. DNA methylation on CG residues is considered a long term method of gene repression. In this paper, Stroud et al. characterise newly-described methylation on CA motifs in DNA and its role in the maintenance of transcriptional memory. They suggest that CA methylation may allow neurons in the developing mouse brain to carry an imprint of early exposures and transcriptional states, recruiting methyl binding proteins to poorly transcribed areas of the genome and maintaining repression throughout development. Original Article

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CRISPR gets crisper: Editing DNA at the single-base level

by Robin Floyd

Life, for all its complexity, is built upon a relatively simple code, comprising only four letters – the chemical bases in the DNA molecule, adenine (A), guanine (G), cytosine (C) and thymine (T) – in intricate sequences many millions of letters long. Ever since the discovery of DNA, a holy grail for biologists has been the ability to re-write gene sequences to our own purposes. In recent years, the genome-editing technology known as CRISPR has made several leaps forward in this regard.

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Cracking the human genetic code: a scientific breakthrough amidst ethical dilemmas

by Lorenzo Orietti

Since its advent, CRISPR-Cas9 has revolutionised scientific research allowing scientists to precisely modify specific genomic regions in different species and in a variety of biological systems. In the last few months, two articles published in Nature took this technology a step further and reported its first ever application to viable human embryos.

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Unboiling egg whites is only the beginning

by Cally Xiao

More than two years have passed since researchers pioneered a technique to unboil egg white proteins, resulting in a media frenzy that intrigued the public. This technique is now being applied to explore other avenues of protein research, and has the potential to be a game-changer in the pharmaceutical industry.

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Frozen Images: how cryo-electron microscopy won the 2017 Nobel Prize for chemistry

by Robin Floyd

At the chemical level, all life is built upon the interplay of complex molecules; a tiny, intricate universe whose inhabitants remain mostly invisible to us. However, a technique called cryo-electron microscopy has enabled scientists to extract images of biological molecules at an unprecedented level of detail, for which Jacques Dubochet, Joachim Frank and Richard Henderson were recently awarded the 2017 Nobel Prize for chemistry.

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CRISPR/Cas gene editing in lab-grown mini organs: The intersection of two new applications to study hard-to-tackle diseases

by Cally Xiao

CRISPR/Cas gene editing technology has taken the world by storm, while lab-grown mini-organs, also known as organoids, have steadily grown in their experimental potential to model their respective organs. Recently, a few research groups have started to combine both techniques, such as the team led by Dr. Deyou Zheng at the Albert Einstein College of Medicine in the United States, who used CRISPR/Cas to study genetic implications of autism in brain organoids. Combining these techniques opens up new possibilities to study diseases and uncover new therapeutic targets.

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