Nýsköpunarsjóður námsmanna gerir fjórum líffræðinemar og BS líffræðingar kleift að verkefnum um skordýr á Íslandi við Líffræðistofu Háskóla Íslands nú í sumar.

Við höfum áður fjallað um maurarannsóknir en auk þess er kastljósinu nú beint að lúsmýi og ávaxtaflugum. Það eru nýlegir landnemar hérlendis. Lúsmýið er alræmt fyrir bit og almenn leiðindi, en ávaxtaflugur eru dýrkaðar og dáðar vegna fegurðar sinnar og fengileiks. Sumir eru reyndar smeykir við ávaxtaflugur, en þær bíta ekki fólk, bera ekki sjúkdóma og verða bara til ama ef þær verpa í bananann sem við gleymdum undir ískáp.

Í lúsmý verkefninu er ætlunin að kanna hvenær sumarsins þær koma fram, hvort um sé að ræða einn eða tvo toppa klaksins, hvaða búsvæðum flugurnar klekjast helst úr og hver dreifing þeirra á landsvísu er. Beitt verður aðferðum skordýrafræði og stofnerfðafræði. Hér að neðan eru myndir af klakgildrum og vettvangi rannsókna í Kjósinni.

We have started a collaboration with Benedikt Hallgrimsson and his colleagues at University of Calgary, Marta Vidal-Garcia and Avrille Aiello.

They are scanning one year old Arctic charr that Sarah Steele raised in her plasticity experiment. That study focused on comparing morphological differences and plastic responses between derived and ancestral populations of charr, to understand differences in growth, allometric changes in shape and inheritance of these traits.

The pilot project with the Hallgrimsson lab focuses on comparing three morphs, the anadromous charr from Fljota (putative ancestral morph) and two derived morphs from Lake Thingvallavatn, the Large Benthic and Planktivorous charr. They were all raised on the same diet, and are similar in size. First scans from Avrille and Marta, of an LB individual, are shown below.

The top figure is lateral view (with an angle slightly from the front) and the lower figure is a view from the top of the head (first vertebrae can be seen on the right).

The fishes were about 1 year old when killed and frozen. Fixed in 10% NPF for 10 days, prior to CT scanning.

In this phase of the project we will scan 20 fishes per morph, and characterize the diversity in shape of the feeding related bones, snout area and the cranium.

And hopefully be able to scan the other treatment, wild fishes and progeny from crosses in the future if funding becomes available.

Trancriptional co-option, transcriptional decay and the principles of regulatory evolution.

Arnar Pálsson, Institute of biology, University of Iceland

Marcos A. Antezana, Institute of biology, University of Iceland

PALSSON A. & ANTEZANA M. 2017: Transcriptional co-option, transcriptional decay and the principles of regulatory evolution. Abstract. - In: W ERTH S. & O BERMAYER W. (editors). Lichen Genomics Workshop II. Institute of Plant Sciences, University of Graz, Austria. 2–5 November 2017. - Fritschiana (Graz) 85: 32–34. - ISSN 1024-0306.

Regulatory evolution is important for adaptive evolution and the emergence of novelties, in part because regulatory mutations tend to be less pleiotropic than changes in exons. The functional properties of regulatory elements, e.g. short, degenerate motifs, for multiple activators and repressors, dictate the evolution of regulatory DNA (Wray et al. 2003). Stabilizing selection on transcription may explain the evolutionary turnover of transcription factor binding sites (TFBS) in enhancers (Ludwig et al. 2000). Genes have been recruited for multiple functions during evolution, by a process called transcriptional co-option (TC) (True and Carroll 2002). In TC a mutation in a gene (here called focal gene), not previously expressed in a specific tissue or cell population during development, turns the gene on in that tissue and the responsible allele is fixed in the population. As new TFBS arise easily via mutation, it was proposed that any transcription factor can co-opt (influence the transcription of) any gene in the genome (Prud’homme et al 2007). Here we define the opposite scenario, evolution by transcriptional decay (TD). In TD, a mutation reducing strongly the transcription of a focal gene in tissue or developmentally specific fashion is fixed by positive selection. An example of TC would be the recruitment of various crystallins to the vertebrate lens (Piatigorsky 2006), and of TD the loss of Pitx1 expression in pelvic structures in stickleback (Shapiro et al. 2004). Here we will use transcriptional decay and co-option as a prism to explore the principles of regulatory evolution.

TC or TD can arise by mutations in either trans-factors (TF) or cis-elements (figure part A). While we focus on mutations in cis, changes in the structure or tissue specific concentration of a TF can affect expression of a focal gene. Such changes are expected to be pleiotropic, with changes in expression of targets of that TF (if changes are in TF level, then the effects will be more circumscribed). Changes at the level of cis-elements will be less pleiotropic. Disruption of TFBS can for example either increase or decrease expression of the focal gene, depending on whether the TF that binds that TFBS represses or activates transcription. The complementary argument applies for mutations that generate TFBS; TC can occur by gain of an activator binding site affecting the focal gene. And in TD a gain of a binding site for repressor near the focal gene.

Regulatory mutations can be pleiotropic. In one scenario, a mutation alters the expression of two or more genes in the same chromosome region. If the fitness increase of the increased expression of the focal gene outweighs the fitness reduction of its chromosome neighbors (figure, part B), then TC can occur. The stronger the selection, the more serious the regulatory side effects can be. After fixation of such a mutation, we anticipate rounds of refinement where the deleterious expression of nearby genes will be alleviated, e.g. by loss of activator sites or gain of repressor sites (figure, part B). Other regulatory changes (miRNA binding sites, RNA degradation etc) may play a role, and the complementary case when reduced expression of two or more genes is favored will adhere to the same principles. Similar mechanistic and evolutionary logic will also be apply if adaptive expression increase of a focal gene in a tissue, leads to increased expression of the gene in other tissues.

The central principles discussed here are, i) mutations disrupting TFBS can lead to beneficial changes in gene expression, ii) cis-regulatory mutations can be pleiotropic, affecting multiple genes and potentially tissues, iii) the likelihood of fixation of such pleiotropic mutations depends on the strength of selection, iv) natural selection is likely to alleviate such side-effects by favoring modifiers (e.g. in cis or trans). Finally, these principles are likely to apply more generally, to gain and decay of associations between trans-regulators and regulatory motifs in DNA, RNA and proteins. For instance regulatory systems like those controlling mRNA splicing, export, stability and localization, translation, protein maturation and modifications and other cellular regulatory cascades.

Acknowledgements. We thank Silke Werth and other organizers of the Lichen Genomics Workshop.

References

Wray G.A., Hahn M.W., Abouheif E., Balhoff J.P., Pizer M., Rockman M.V., Romano L.A. 2003: The evolution of transcriptional regulation in eukaryotes. Molecular Biology and Evolution.20: 1377-1419.

Ludwig M.Z., Bergman C., Patel N.H., Kreitman M. 2000: Evidence for stabilizing selection in a eukaryotic enhancer element. Nature. 403: 564-567.

True J.R., Carroll S.B. 2002 Gene co-option in physiological and morphological evolution. Annual Review Cellular and Developmental Biology. 18: 53-80.

Prud'homme B., Gompel N., Carroll S.B. 2007 Emerging principles of regulatory evolution. Proceedings of the National Academy of Sciences U S A. 15: 8605-8612.

Piatigorsky J. 2006 Evolutionary genetics: seeing the light: the role of inherited developmental cascades in the origins of vertebrate lenses and their crystallins. Heredity. 96: 275-277.

Shapiro M.D., Marks M.E., Peichel C.L., Blackman B.K., Nereng K.S., Jónsson B., Schluter D., Kingsley D.M. 2004 Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks. Nature. 428: 717-723

Nordic Committee on Bioethics Conference: Facing Death - End of life decisions

Should end of life care for incurable ill patients include the possibility of euthanasia or physician-assisted suicide? Assisted death or euthanasia are not allowed in any of the Nordic countries, however, surveys show that an increased proportion of the public supports this.

In this summary I would like to raise a few objections about the evaluation system that has been in use at the University of Iceland for a few decades now. The objections fall into four main categories. First are concerns about the role and output of Universities. Second is the problem of trying to measure the unmeasureable. Third is the increased corporatization of western universities and the fourth concerns the specifics of the Icelandic evaluation system. My conclusion is that the evaluation system used at the University of Iceland is fundamentally broken, should be disbanded and a new structure put in place to evaluate the performance of the teachers/researchers at the University.

I. Roles of Universities.

First I would like to highlight the roles of Universities in the modern age. Scholars, like our former rector Pall Skulason, have categorized three major roles for Universities. Skulason identifies the French (Napoleonic) university, a utilitarian institution aimed at serving the nation, solving problems at hand (concerning health, agriculture, industry, army) – often with top down administration, the German (Humboltian) university which is concerned with gathering knowledge for its own sake – letting basic research run free so to speak – obviously with the scholars them selves in charge of administration, and the English (Newtonian) university, aimed at providing the government with skilled personel to run an empire (administrators, officers, priests, lawyers, bankers etc) – the board of these universities obviously respond to the needs of governments.

Continue reading 'The University of Iceland individual evaluation system'»

Nordic committee on bioethics in junction with the Norwegian biotechnology board, organized a miniconference on the new Crispr/Cas technology and the genetic modification of human embryos. The conference was held at the University of Oslo, June 2nd. The title was Gene therapy and human germline editing: new opportunities, new challenges.

We heared great talks by Fredrick Lanner, Gunnar Kvalheim, Johanna Ahola-Launonen, Jacob Wang, Anne-Marie Gerdes and Nils-Eric Sahlin, and were then given the task to summarize the meeting.

I will not attempt to do that here, because my notes were incomplete and the things I said didnt quite follow the notes (either a plus or minus, Im not sure).

The new technologies open some new opportunities, for studying the effects of mutations and systems on human cells and early development. There is also the future possibility of using this technology to modify the human cells, to correct serious errors in DNA to treat (somatic) or to prevent (germline) devastating diseases. The current seems to be flowing in that direction, granting of course that the technology will become efficient enough and side effects can be minimized. In fact this is the first moment that I felt that steps towards germline could and perhaps should be taken.

To counter, there were several issues raised with further developing the technology for modifying human embryos, including the slippery-slope argument, side-effects, dont-mess-with-nature, and a few others. But in general they are no unique to this technology.

The only new concept is that we may alter the genetic makeup of our species directly with this new technology. But in fact we have been changing our genetic makeup, indirectly with choices in lifestyle and human history and technological development.

In sum, I learned a lot but am still confused about the subject.

Those who want to read more should check out a new statement and report by the Danish council on ethics which summarized these issues quite well.

Statement from the Danish Council on Ethics on genetic modification of future humans (2016)

Sorry, this entry is only available in Icelandic.

Post doc available: The role of transcriptional and regulatory changes during compensatory evolution

Which principles influence the rewiring and tuning of gene regulatory networks? How do those network react to genetic perturbations? We are seeking a post-doc to tackle those and related questions in project utilizing populations of Drosophila that have undergone compensatory adaptation using experimental evolution and artificial selection. The project involves the analysis of tissue specific RNA-seq and numerical analyses. The ideal candidate is strong in evolutionary genetics, statistical and bioinformatic analyses and with capable hands for molecular biology. Excellent communication skills, main focus on writing, are required, as is a solid publication record. The candidate will be encouraged (and given time) to develop their own research program.

The project involves a collaboration between University of Iceland and McMaster University, with approx. 3/4 of the work conducted in Iceland and 1/4 in Canada. Those interested are asked to send a cover letter detailing research interests and experience, a current CV, and contact details for three professional references by April 1st. Anticipated start date is Fall 2016, but this is flexible. The position is funded by the Icelandic Research fund (for 2 years), salary commensurate with qualifications.

The University of Iceland is the leading research institute in the country, and groups at the Institute of biology (luvs.hi.is/institute-biology) and Biomedical Center (lifvisindi.hi.is) study genomics, evolutionary, developmental, cellular and molecular biology. The shared facilities include High throughput sequencers, various specialized molecular biology equipment and computer clusters. The University is an equal opportunity workplace with strong combination of international and domestic scientists.

Learn more about the work in the Palsson (uni.hi.is/apalsson) and Dworkin (http://www.biology.mcmaster.ca/dworkin/) labs.

Please send applications and/or inquiries to apalsson@hi.is.

This project is built on work on indel polymorphism in the even skipped stripes 3+7 enhancer and on the conditional effects of genetic backgrounds on wing mutations.

Palsson A, Wesolowska N, Reynisdóttir S, Ludwig MZ, Kreitman M (2014) Naturally Occurring Deletions of Hunchback Binding Sites in the Even-Skipped Stripe 3+7 Enhancer. PLoS ONE 9(5): e91924. doi:10.1371/journal.pone.0091924

Chari S, Dworkin I (2013) The Conditional Nature of Genetic Interactions: The Consequences of Wild-Type Backgrounds on Mutational Interactions in a Genome-Wide Modifier Screen. PLoS Genet 9(8): e1003661. doi:10.1371/journal.pgen.1003661

This Friday I enjoyed the privilege of being a Phd. examiner for the first time. The (un)fortunate individual was Ari Jon Arason, who has been working on the functional role of human bronchial derived basal cells in regeneration and fibrosis within the Faculty of medicine.

Emma Rawlins from the Gurdon Institute was the other examiner, and she did a marvelous job. She works in the field of stem cell biology and has a fabulously interesting paper on biophysical model of basal stem cell populations (Watson JK, Rulands S, Wilkinson AC, Wuidart A, Ousset M, Van Keymeulen A, Gottgens B, Blanpain C, Simons BD and Rawlins EL (2015) Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow Turnover Airway Epithelium. Cell Reports 12, 1-12)

After her questions all I could ask about was evolution of lungs, and stem cells and variation in lung structures between individuals, and transcription factor isoforms of course. All in all this was an enjoyable experience. The work was well executed and interesting, his thesis was a good read and corduroy gowns a lot less awful than I imagined. For some reason the University of Iceland has adopted very formal guidelines for PhD. defenses, involving gowns, parading and verbose introductions and declarations. At least the Rector does not have to sip champagne with every new Phd, as the earlier guidelines stipulated.