In this project, you will use single-molecule techniques to label mRNA and DNA in (live and fixed) Drosophila embryos and fixed embryonic bodies. You will also use super-resolution microscopy to visualize protein condensates. Co-localization dynamics reflecting DNA-protein bindings and DNA looping events will be detected, analyzed, and used to test computational models of gene transcription.

Qualification:
MSc degree (or equivalent) in Biology, Biophysics, or Bioengineering

Experience in one or more of these areas: (1) molecular cloning, (2) imaging, (3) image analysis (using Matlab/Python/Java), (4) microfluidics, and (5) computational modeling.

How to Apply?
Send (1) your CV, (2) summary of research experience, and (3) email addresses of at least 2 references to ezzat.el-sherif@fau.de. Title your email ‘Transcription PhD Position’.

salary Grade.: E13
Total Time: 3 Jahre
Start: 01.01.2020.
End: 31.3.2020.

Address:
Dr. El-Sherif, Ezzat
Department Biologie
Professur für Zoologie (Entwicklungsbiologie) (Prof. Dr. Klingler)
Telefon 09131/85-28068, Fax 09131/85-28040, E-Mail: ezzat.el-sherif@fau.de

Searcg link https://metagraph.ethz.ch/search 

Pre-print https://www.biorxiv.org/content/10.1101/2020.10.01.322164v4 

Address of the bookmark: https://metagraph.ethz.ch/

Bdelloid rotifers are small animals well known for their ability to survive in harsh conditions. They can endure extreme dehydration by entering a state of dormancy and then revive when water becomes available again. Scientists have always been interested in the degree to which these animals resist radiation, since radiation can severely damage DNA by causing both of its strands to break. Interestingly, Adineta vaga's ability to survive radiation may be connected to the way in which it tolerates drying out, as dehydration can also damage DNA. The rotifer probably evolved strong DNA protection and repair mechanisms primarily as a response to its severe environment. Its resistance to radiation is merely a byproduct of adapting to the cycles of drying and rehydration.

In order to find out more about this ability, the researchers subjected A. vaga to proton radiation and then examined what effect it had on its chromosomes. The radiation caused serious damage, resulting in hundreds of breaks in the DNA. For the vast majority of organisms, such extensive chromosome damage would be disastrous; it's similar to going through an instruction manual in a shredder and ending up with a large number of separate fragments. The scientists believed that the rotifers would repair their chromosomes before producing offspring. However, what they discovered was unexpected: some of the broken pieces of chromosome did survive and were passed on to the next generations, where the repair process continued.

The discovery took on even greater interest when the scientists examined the offspring of the irradiated rotifers. Rather than observing the same DNA damage in all the generations, they found different sized sections missing and evidence that some of the genetic regions which had been lost were being slowly restored. The researchers proposed that the rotifers use a repair mechanism known as Break-Induced Homologous Extension Repair, or BIHER. In simple terms, a broken piece of DNA can locate a matching sequence on the other chromosome and use it as a guide to rebuild itself. If the damage is beyond what can be repaired in one generation, the repair process can continue in the next.

What makes the rotifer's method of repairing DNA so unusual is that, normally, we consider DNA repair to take place immediately after damage has occurred, with the cell rapidly repairing the damaged DNA. In A. vaga, however, the repair process can be a lot longer. Certain pieces of chromosome survive the initial damage, are inherited, and then serve as the basis for further repairs in later generations. It's as if one generation begins mending a broken book, the next one continues the work, and another eventually completes the job until all the missing parts have been restored.

One reason why this might work is that bdelloid rotifers have holocentric chromosomes. Rather than having a single point, as most chromosomes do, which controls movement during cell division, the ability to move is distributed along the entire length of their chromosomes. As a result, fragments of chromosomes are sometimes able to retain the parts that are necessary for them to move and divide, and this may account for how broken pieces of chromosome can last long enough to be passed on and then repaired.

This finding could have implications that go beyond those concerning rotifers. Scientists are interested in understanding how genomes cope with severe chromosome damage, for example in the case of chromothripsis, where chromosomes break and are then reassembled in new configurations. Investigating A. vaga could help us to learn how cells manage large genetic issues. Moreover, its high resistance to radiation might also prove useful in research into extreme environments, such as the radiation hazards encountered on long space missions. However, these are ideas for future investigation; at present the rotifer's DNA repair mechanism cannot be used to protect people from radiation.

What is perhaps the most interesting aspect of this discovery is that the rotifer's remarkable ability could have developed for a very simple reason. Since an animal living in moss constantly undergoes periods of drying out and then getting wet again, the same mechanisms that protect its DNA when it is dehydrated might also enable it to survive radiation which would damage most other animals. Therefore, the rotifer probably did not evolve solely in order to resist radiation; instead, it became extremely good at coping with the difficult conditions it encounters, and radiation resistance was just a byproduct.

The case of Adineta vaga demonstrates that survival does not always mean avoiding damage; on some occasions it involves being able to recover from damage which appears to be impossible to repair. This small animal can survive having its chromosomes broken into many pieces, retain some of those pieces, pass them on to its offspring, and continue to repair them over successive generations. Although we generally regard DNA as something fragile that must always remain intact, the rotifer indicates an alternative possibility: perhaps a genome does not have to be perfect in order to survive, since sometimes the pieces last long enough for life to reassemble them, bit by bit, generation after generation.

Ream more at https://www.science.org/doi/10.1126/sciadv.aee0891

Address of the bookmark: https://github.com/b-brankovics/grabb

http://www.stratosgenomics.com/stratos-genomics-technology

Blobsplorer is unlikely to be of use on its own as it requires contig data to be supplied in a format that involves considerable preprocessing (see below for a description). The easiest way to use Blobsplorer is as part of a workflow using scripts from here.

Address of the bookmark: http://nematodes.org/martin/blobsplorer/blobsplorer.html

http://novelseq.sourceforge.net/Home

Paper at https://www.ncbi.nlm.nih.gov/pubmed/20385726

Address of the bookmark: http://novelseq.sourceforge.net/Home

Address of the bookmark: https://github.com/Reedwarbler/GAPPadder