SciBlogs

Posts Tagged research blogging

Coiling bacterial DNA Grant Jacobs Aug 24

7 Comments

A chain of proteins hold bacterial DNA in a compacted spiral.

You and I are eukaryotes. Our cells have nuclei, repositories that contain our DNA and the proteins that read them to produce an RNA copy of them.

HeLa cells*** stained for DNA (Source: Wikimedia Commons.)

HeLa cells* stained for DNA (Source: Wikimedia Commons.)

In earlier articles, I’ve mentioned in passing how the enormous length of DNA in our cells is fitted into a nucleus. Our DNA, all 2 metres of it, were you to stretch it out end-to-end — is fitted within a nucleus with a diameter of roughly 6-10 micrometres, about one-millionth of a metre.

The trick is that a DNA molecule is very skinny — it’s only about 2 nanometers wide (2 billionths of a metre wide). Wrap that up around a something handy and it’ll be quite compact.

The ‘something handy’ in eukaryotes are histone proteins. Eight histone proteins associate to form a disk-shaped octamer, wrap DNA almost twice around it and you have a structure called a nucleosome. Read the rest of this entry »

Preserving endangered species – of gut microbes Grant Jacobs Aug 04

3 Comments

A recent paper argues for the need to preserve the gut microbes found in ancient rural populations.

We talk about preserving rare species, sometimes arguing that they might have medicinal value.

BF-village-scene

Some species produce different types of venom, that when applied properly can have medicinal uses.

Certain plants have toxins that they use as part of a defences against insects.

A recent paper I strayed upon showed another class of organisms that might have useful properties that are endangered: the microbes in the gut of people from ancient rural populations.

The abstract of De Filippo and colleagues article closes with,

This study investigates and compares human intestinal microbiota from children characterized by a modern western diet and a rural diet, indicating the importance of preserving this treasure of microbial diversity from ancient rural communities worldwide. Read the rest of this entry »

Epigenetics and 3-D gene structure Grant Jacobs Aug 03

1 Comment

DNA methylation controls the binding of proteins that control the 3-D structure of genes.

This is a lightly edited version of an article I wrote as a guest on Alison’s blog over a year ago, looking back a couple of years to show something of what epigenetics was bringing to genome biology. The science has advanced further again since, but I’m nicking it back onto my blog (with Alison’s permission!) as it sets up other articles I would like to write.

Human karotype. (Source; Wikimedia Commons.)

Human karyotype. (Source; Wikimedia Commons.)

My article followed one Alison wrote about epigenetics. I’d suggest you read that first, as it will help!

While I’ve simplified quite a bit of the science to make things a bit clearer, it is a lot to take in, but persevere and you might get a glimpse of some of what this epigenetics fuss it really all about. (Feel free to ask questions in the comments section.)

I wanted to introduce an aspect of epigenetics that interests me: specifying the use of genes through forming different chromatin loops. In the case I’m going to look at the structure of the gene depends on which parent the copy of the gene came from.

Humans are diploid: we have two copies of each chromosome, one from each parent, except in males there is usually only one X and one Y chromosome (but two of all the others). Ignoring the sex chromosomes in males, having two of each chromosome also means that we have two copies of each gene. Each of the two genes making up a pair of corresponding genes, one from each parent, is called an allele. The two alleles of a gene make up the genotype of that person for that gene.

For most genes, when the gene is needed, both alleles are expressed and roughly the same amount of the RNA each allele codes for is made. But in some cases, evolution has selected that one of the two alleles should be switched off.

Tortoise shell cats are an example of mosaic X-chromosome inactivation (Image source: Wikimedia Commons.)

Tortoise shell cats are an example of mosaic X-chromosome inactivation (Image source: Wikimedia Commons.)

Alison described one example of this in her article: dosage compensation in females “corrects” for having twice the number of X chromomome genes as needed by switching one copy off. Recapping on what she was saying, in the case of switching off the “extra” copy of the genes on the “second” X chromosome in females, the choice of if the copy from the father (paternal allele) or from the mother (maternal allele) is inactivated is random. The choice made is inherited in each cell line once that choice is made. Because there are many cells, each making a separate random choice of which allele to switch off, most female mammals are mosaics, with a mixture of cells with an active paternal X chromosome genes and with an active maternal X chromosome genes. (I believe, rodents and marsupials are exceptions to this rule.)

One example of this are tortoise shell cats. The choice of expressing the black or orange alleles for fur colour are randomly chosen over the cat’s body.

Read the rest of this entry »

The roots of bioinformatics Grant Jacobs Aug 02

7 Comments

I’d like to bring to wider attention an article series, The Roots of Bioinformatics.

The roots of prairie plants (Source: Wikimedia Commons.)

The roots of prairie plants (Source: Wikimedia Commons.)

Hold up.

Before experimental biologists run away, you’re some of the people I’d like this to reach!

At a recent bioinformatics meeting I attended, a senior experimental biologist from overseas commented to the effect that it was hard for bioinformatics researchers to build their own careers, to publish their own papers. My take on his comment was that he was referring to the tendency of experimental research to treat the bioinformatics as a service, seconding the work or linking to service centres, rather than treating bioinformatics researchers as collaborators, stand-alone groups in their own right.

I’m not about to argue the ins and outs of that here, but to draw attention to understanding the origins of bioinformatics, and hence it’s deeper alliance with biology.

One senior scientist at that meeting showered praise on Lincoln Stein for “his pioneering work in bioinformatics” (I’m paraphrasing here). I gritted my teeth and bit my tongue. Stein certainly contributed in a fine way to the human genome project, but he was no pioneer of bioinformatics.

I thought it very telling that a senior biologist would think that.

It made me think that some (still) think of bioinformatics as a young field that emerged as a consequence of the service needs of the genome projects. I worry that an overly service-oriented view of bioinformatics prevails because of this.*

It’s a topic I touched on in The mythology of bioinformatics. My article doesn’t attempt to give a history of the field, as this series in PloS Computational Biology I am introducing here does, but briefly points to early work whose that could clearly be recognised today as being bioinformatics, and highlights other issues that I felt at that time were leading to misunderstanding.

By contrast, the new series in PloS Computational Biology is squarely aimed at giving an anecdotal narrative history of the field; another approach to better understanding bioinformatics today and what it has to offer to biology.

David Searl’s editorial introduces the Roots of Bioinformatics series, starting with a little light philosophy on the dual roles of tools and knowledge, bioinformatics combining the two.

The  second paper in the series, Russell Doolittle’s The Roots of Bioinformatics in Protein Evolution is now available. I like the approach he takes, working from the biological issues of the day, looking at how issues from the pre-electronic approach to protein biology lead to protein bioinformatics.

I would like to like to see this series more widely read, beyond preaching to the choir, as it is being published within a specialist journal.

My only worry is that the series will prove too patch-meal or specialist for those outside of the field. Hagen’s article might be useful to some (free PDF copy).

It will be interesting to see what the rest of the series brings, and I welcome that attention is being paid to the deeper origins of the field.

Footnotes

* I’m not saying that services don’t have a role, they certainly do, but that there is more to the field than just services.

ResearchBlogging.orgReferences

Searls, D. (2010). The Roots of Bioinformatics PLoS Computational Biology, 6 (6) DOI: 10.1371/journal.pcbi.1000809 (open access)

Doolittle, R. (2010). The Roots of Bioinformatics in Protein Evolution PLoS Computational Biology, 6 (7) DOI: 10.1371/journal.pcbi.1000875 (open access)

Hagen JB (2000). The origins of bioinformatics. Nature reviews. Genetics, 1 (3), 231-6 PMID: 11252753 (subscription, but free PDF copy available on-line)

Other articles on Code for life:

Loops to tie a knot in proteins?

Who has the most bioinformatics scientists?

Testing common ancestry to all modern-day life

Consumer brain-computer interface

Forgetting older science

Loops to tie a knot in proteins? Grant Jacobs Jul 30

6 Comments

Most proteins fold onto themselves without forming knots. A minority form a “topologically entangled conformation”, a knot.

Proteins are strings of amino acids, chained together one after the other.

(Source: WIkimedia Commons.)

(Source: WIkimedia Commons.)

The properties of proteins depends on their specific three-dimensional fold, how the chain of amino acids are arranged in space.

When proteins are first made by reading the RNA copy of a gene, the order of the adjacent triplets of RNA bases (letters of the RNA code) specify a specific order of amino acids, one amino for each particular triplet of bases.

This initial chain of amino acids is just that, a linear chain.

Proteins fold through the physical properties of the particular sequence of amino acids making up the protein inducing a particular collapsing of the protein on itself in water.

For the vast majority of proteins this collapsing on itself does not involves a portion of the chain threading itself through another portion of the chain to form a knot.

Intuitively this makes sense; self-knotting of a protein chain would be more finicky that simply placing portions of chain adjacent to other portions of the chain.

A few proteins, however, manage to pull off this self-knotting feat.

Being able to accurately predict the folding of a protein from it’s amino acid sequence, to solve the “protein folding problem” would open door to designer enzymes and vastly increase our understanding of life through having available the detailed chemical arrangement of proteins in 3-D.

In this cartoon of a protein, the grey tubes represent loops connecting the more compact helical and ribbon (red arrow) regions of this small portion of a protein (Source: Wikimedia Commons.)

In this cartoon of a protein, the grey tubes represent loops connecting the more compact helical and ribbon (red arrow) regions of this small portion of a protein (Source: Wikimedia Commons.)

Examining knotted proteins, with their potentially more finicky folding requirements, might be another way to explore the detailed basis protein folding.

What features might guide self-knotting in proteins and can they teach us something about how proteins fold?

European computational biologists compared proteins that form knots and those that do not, looking for features that might be associated with knot formation.

For the most part the amino acid sequence of the proteins did not distinguish knotted proteins from those without knots.

Comparing the 3-D structures of proteins, in particular those with similar overall folds but with one case being knotted and the other not, their work suggested particular loops on the surface of some the proteins examined are a feature common to knotted proteins not found in unknotted proteins.

These might be, in their words, “knot-promoting” loops, in some way these loops may be aiding the chain in threading through itself.

(Source, Fig 1 of Reference.)

(Source, Fig 1 of Potestio et al, see References.)

I’ve no doubt that researchers will now look very closely at these particular protein loops and see if they do in fact promote the formation of a protein knot.

ResearchBlogging.orgReferences

Potestio, R., Micheletti, C., & Orland, H. (2010). Knotted vs. Unknotted Proteins: Evidence of Knot-Promoting Loops PLoS Computational Biology, 6 (7) DOI: 10.1371/journal.pcbi.1000864

Other articles in Code for life:

Rex and The Wrong Trousers – uncanny resemblance?

Making the most of lousy book reviews on Amazon

Consumer brain-computer interface

Developing bioinformatics methods: by who and how

Testing common ancestry to all modern-day life

Honey’s anti-bacterial properties found? Grant Jacobs Jul 14

8 Comments

New research suggests that (some of) the secrets to honey’s anti-bacterial properties may have been revealed.

A Dutch team of microbiologists propose that the anti-bacterial properties of the honey they tested come down to four chemicals and one general property:

Honey comb; near the top-centre bees can be seen entering the combs (Source: Wikimedia Commons.)

Honey comb; near the top-right bees can be seen entering the combs (Source: Wikimedia Commons.)

Sugars High concentrations of sugars have long been known to have anti-bacterial properties and are used in preserving food.

The best known effect is by soaking up water. Bacteria, like most living things, need water. Soak up the water and they’ll dehydrate.

Ever tried to clean up a wine spill in the carpet by dribbling some water over the stain, then sprinkling salt over the water? You’ll know how the salt sucks up the water from the carpet.

In a similar way, high concentrations of sugar outside cells, can suck water out of the cells or absorb other moisture that’s around. This works through creating an osmotic gradient, where the moveable part — water — moves to balance the low concentration of water outside the cell, dehydrating the cell.

H2O2 Hydrogen peroxide is a bleach used in making paper among other things. Household bleach kills bacteria, so does hydrogen peroxide.

Read the rest of this entry »

Temperature-induced hearing loss Grant Jacobs Jul 14

2 Comments

Two recent studies independently report mutations in the otoferlin (OTOF) gene are the cause of a rare temporary hearing loss caused by a high body temperature.

Ear-120px

I have a hearing loss, and if I spot research on deafness when updating papers for my own research (see Footnote of previous post) I often take a peek.

Tonight I learnt that some people have deafness that is dependent on their body temperature, with a high temperature (say, a fever) inducing deafness. They recover some time after their body temperature has returned to normal.

In some ways it’s quite quirky, but knowing how molecules interact I can imagine how this might be possible.

The study I ran into was a Chinese study examining a collection of 73 Han Chinese patients with auditory neuropathy*. During this study, they uncovered a case of temperature-dependent hearing loss:

However, his hearing was affected by a slight change of body temperature. His mother found that his hearing in the morning is generally better than in the afternoon, and temperature measurements showed that his body temperature in the afternoon was generally 0.1-0.6 Π [˚C?] higher than that in the morning.

They tested his hearing loss, raising his body temperature during an extended hospital visit and found that

When his body temperature rose above 36.5°C, the boy’s hearing loss was severe (70-80dB HL) and this symptom could last for a whole day.

Read the rest of this entry »

Boney lumps, linkage analysis and whole genome sequencing Grant Jacobs Jul 06

1 Comment

We all have our lumps, the quirky features we develop with time.

Some of these are bone spurs, extra growths of bone.

These can be caused from damage to joints, like the lumpy joints seen in elderly people with arthritis. Bone spurs from differing causes can develop in many parts of the body, spine, toes, heel and hands.

Most bone spurs are associated with damage and old age, but some have genetic origins.

Figure 1A from Sobreira et al. (see References)

Figure 1A from Sobreira et al. (see Reference)

Metachondromatosis is a rare disorder that affects bone growth, where benign bone tumours produce lumps, mostly on the hands and feet.*

These lumps develop in children, with some of them reducing or resolving over time, others persisting.

Nara Sobreira and her colleagues set out to find genes that might cause this disease using a new approach that exploits sequencing of the whole genome of one patient.

Genetic changes that cause a disease can be as small a changing a single base in the roughly three billion bases in our DNA.

We have many, many differences that make us unique.

The art of locating the cause of a genetic disease is to determine which of those many changes from a lot of DNA is the one that has a role in causing the disease.

Read the rest of this entry »

Autism genetics, how do you copy? Grant Jacobs Jun 10

6 Comments

Subtitle: Recent research identifies many changes in copy number that may point to genes that cause or are associated with autism.

In order to verify that important information has been conveyed over radio, the sender might ask “how do you copy” or, more briefly, “how copy” asking the receiver to tell the sender the information they received for confirmation.

Copying genetic information accurately from one generation to another is important. Altered (mutated) genes, or adjacent regions that control how genes are used (regulatory regions), can interfere with the function of the affected portion of the genome.

When geneticists talk about ‘copy number’, they are referring to a kind of change where the number of copies of a portion of the genome has been altered. Portions of the genome that have different numbers of copies in different people’s genomes are referred to as copy number variations, or CNVs for short.

Copy number variations can be extra duplicate copies of a portion of the genome,* or deletion from loss of genetic material.

Duplications and deletions can involve portions of the genome much larger than a single gene, or short stretches much smaller than a gene. The study just reported looks for large CNVs, big enough to include a whole gene or several genes (30-500 kilobases).

For some diseases changes in just one or a small number of genes can explain the genetic causes of the disease.

In the case of autism, while it is highly heritable (~90%), to date no one genetic change is found in a large portion of autistic people.

Instead, it seems that we might expect a large number of different changes, each found in a small proportion of the total autism cases, that taken together might explain the genetic causes of autism.

Read the rest of this entry »

I remember because my DNA was methylated Grant Jacobs May 29

2 Comments

Our memories keep our yesterdays, our friends’ faces, the distinctive smell of previous partners, if we’ve read that book before, what clothes you wore to the party.

in_search_of_memory_movie_posterMovies and books have been written about memories. Or the trials not being able to keep them.2

Poets and lyricists evoke them, talk about them and reminiscence over them: “Preserve your memories, they’re all that’s left of you.” (Paul Simon, Old friends/Bookends.)

Is DNA methylation what preserves your memories?

Among neurobiologists are some looking for the basis of memory, how is it that neurons (nerve cells) record an event, a smell, a sight? We know they do, but how?

DNA methylation is one of several ways to control the state of a gene, if it is able to be used or not. Regulation of the state of a gene might be used to define a pattern of responses to signals in a neuron, that can then represent part of a memory.

Read the rest of this entry »

« Older Entries