Postdoc Positions to Study Spontaneous Mutation

| 28 Comments

Announcement of Microbiologist Position at UHAnnouncement of Bioinformatics Position at ASU

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The Cartwright Lab at Arizona State University (Tempe, AZ) and the Zufall and Azevedo Labs at the University of Houston (Houston, TX) are hiring two evolutionary genomics postdocs to work on an NIH-funded project to utilize the unusual nuclear architecture of ciliates to study the rate, types, and fitness effects of spontaneous mutation.

Ciliates are really, really cool beasties.

Unlike most eukaryotes, ciliates have two nuclei. That’s two nuclei in a single celled organism.

It gets cooler than that. One nucleus, the micronucleus, pretty much does nothing, sitting around and waiting for the ciliate to have sex. The other nucleus, the macronucleus, is a copy of the micronucleus and manages all the daily activity of the cell (i.e. transcription). During sex, the macronucleus disappears, and the micronucleus goes through meiosis creating haploid nuclei which get exchanged with another cell. This forms a new micronucleus from which a new macronucleus will be generated. This is why the micronucleus is considered the germline nucleus and the macronucleus the somatic nucleus.

It gets cooler than that. In Tetrahymena thermophila the micronucleus is diploid and has 10 chromosomes. The macronucleus is 45x and has over 20,000 chromosomes; during macronucleus development, the chromosomes basically shatter, duplicate, and reassemble a bunch of times. Like magic!

All this makes Tetrahymena thermophila a nearly perfect system in which to study spontaneous mutation. By maintaining Tt lines in asexual growth, mutations will accumulate in the germline nucleus without any selection operating on them. Thus at the end of 1,500 generations, we will be able to express these mutations and measure their phenotypes and impact on fitness.

For this project we are looking for a wet-lab postdoc to be based in the Zufall lab at UH and a dry-lab postdoc to be based in the Cartwright lab at ASU, but also working with the Azevedo lab at UH. The wet-lab postdoc will be primarily responsible for generating the mutation accumulation lines, while the dry-lab postdoc will be primarily responsible for identifying mutations from genomic data and analysing the phenotypic data. Full descriptions and instructions on applying are below.

Announcement of Microbiologist Position at UHAnnouncement of Bioinformatics Position at ASU

Postdoctoral Research Associate Opening at UH

The Zufall Lab at the University of Houston is seeking a Postdoctoral Research Associate in the area of Evolutionary Genetics to create and study mutation accumulation lines in the ciliate Tetrahymena thermophila. These lines will form the basis of an NIH funded collaboration with the Azevedo (University of Houston) and Cartwright labs (Arizona State University), which will take advantage of the unusual nuclear architecture of ciliates to study the rate, types, and fitness effects of spontaneous mutation.

As part of this project, the postdoc is expected to be able to: develop and culture T. thermophila mutation accumulation lines, conduct genetic analyses and fitness assays on these lines, and interpret data using computational and statistical analyses in collaboration with the Azevedo and Cartwright labs. Candidates should possess a Ph.D. in Evolution or Genetics. Experience with microbial eukaryotes is desirable and skill in computational and statistical analysis is preferred.

Information about the labs involved can be found here: Zufall Lab, Azevedo Lab, and Cartwright Lab.

Applications can be made at jobs.uh.edu (Posting Number: S001408) and must include a cover letter, detailed CV, and names of 3 references. The initial closing date is July 15, 2013, but applications will continue to be accepted and considered until the job is filled/closed.

The University of Houston is an Equal Opportunity/Affirmative Action employer. Minorities, women, veterans, and persons with disabilities are encouraged to apply.

Contact Becky Zufall at [Enable javascript to see this email address.] for more information.

Postdoctoral Research Associate Opening at ASU

The Cartwright Lab at Arizona State University in Tempe, AZ is seeking a Postdoctoral Research Associate in the area of Computational/Statistical Genomics to study evolutionary questions using mutation accumulation lines of the ciliate, Tetrahymena thermophila. These lines are being generated as part of an NIH funded collaboration with the Zufall and Azevedo labs at the University of Houston.

The Cartwright Lab is part of the Center for Evolutionary Medicine and Informatics (CEMI), one of 10 research centers in the Arizona State University’s Biodesign Institute. Research in the Cartwright Lab covers many different questions in population genetics and molecular evolution, at the interface of biology, statistics, and computer science. A majority of our research involves developing, implementing, and applying novel methodologies to study genomic datasets.

As part of this project, the Postdoctoral Research Associate is expected to be able to:

1. Assemble the genomes of the dozens of Tetrahymena thermophila lines from short-read sequences
2. Develop novel, high-throughput methodologies to identify de novo mutations by comparing multiple lines
3. Work closely with collaborators at the University of Houston to develop statistical methods to estimate the phenotypic effects of mutations
4. Present the results of research at meetings, in publications, etc.

Required Qualifications:

Ph.D. in genomics, bioinformatics, or related field

Desired Qualifications:

1. Experience working with microbial genomes
2. Knowledge of programming languages including Python and C++
3. Knowledge of statistical methodologies
4. Experience with short-read sequencing

Application must contain one document which includes

1. Resume/CV
2. Cover Letter
3. Names, addresses, and phone numbers of three professional references

Deadline for applications is July 21, 2013. Applications will continue to be accepted and considered until the job is filled/closed.

For more information see Cartwright Lab, Zufall Lab, and Azevedo Lab.

To apply, forward one document that includes a cover letter, detailed CV, and names of 3 references to [Enable javascript to see this email address.]. Please put the job title in the subject line of the letter.

Arizona State University is an Equal Opportunity/Affirmative Action employer. A background check is required for employment.

28 Comments

Fascinating. This posting appears below, that is farther down, from an older posting so it does not appear at the top of the screen like it should. People can easily overlook this posting b/c they do not see it. Can that be fixed?

Besides allowing spontaneous mutations to accumulate, could this system could be used to generate mutations, for example by X-rays, or EMS…, and then screen for novel phenotypes? This would be similar to how things were done in the massive mutation screens for Drosophila and the zebra fish.

Mark Sturtevant said:

Fascinating. This posting appears below, that is farther down, from an older posting so it does not appear at the top of the screen like it should. People can easily overlook this posting b/c they do not see it. Can that be fixed?

The photography contest announcement is stickied so that it doesn’t fall down the page.

Yes, you could create mutations artificially, but we are interested in the natural distribution and rate of mutations. Some of our preliminary results indicate that ciliates have really low mutation rates, maybe 10 or more times lower than humans.

Eventually, I’ll unsticky the contest page and put a link to this page in its place.

Reed A. Cartwright said:

Yes, you could create mutations artificially, but we are interested in the natural distribution and rate of mutations. Some of our preliminary results indicate that ciliates have really low mutation rates, maybe 10 or more times lower than humans.

Eventually, I’ll unsticky the contest page and put a link to this page in its place.

That is exceedingly interesting. Is that the net mutation rate, after repair mechanisms, or do they seem to have a lower initial rate?

The macronucleus behavior is at least superficially reminiscent of what happens in some, not all but some, human cancer clones, via somatic mutation. Human cancer is a tragic example of evolution at the cellular level (I’ve been saying this for years and now the editors of the New England Journal of Medicine are saying it, too). Although they kill the host eventually if untreated (thus making themselves “extinct”), cancer cells are rapidly evolving population that, by ignoring normal differentiation and regulation, out-compete normal cells for resources and physically disrupt normal tissues. They can mutate at freakishly high rates but remain viable despite highly bizarre genomes. Remember that these are somatic mutations. A small proportion of human cancers arise from germ cell progenitors, or at least show germ-cell like differentiation, but these are all somatic mutations that die out with the cancer clone.

If I understand correctly, ciliates are a fascinating example of a unicellular organism with both germline and somatic mutations. This is very interesting stuff.

Ciliates are of the devil. Add and subtract and multiply the letters until you get 666… and you get 666!

harold said:

Reed A. Cartwright said:

Yes, you could create mutations artificially, but we are interested in the natural distribution and rate of mutations. Some of our preliminary results indicate that ciliates have really low mutation rates, maybe 10 or more times lower than humans.

Eventually, I’ll unsticky the contest page and put a link to this page in its place.

That is exceedingly interesting. Is that the net mutation rate, after repair mechanisms, or do they seem to have a lower initial rate?

The macronucleus behavior is at least superficially reminiscent of what happens in some, not all but some, human cancer clones, via somatic mutation. Human cancer is a tragic example of evolution at the cellular level (I’ve been saying this for years and now the editors of the New England Journal of Medicine are saying it, too). Although they kill the host eventually if untreated (thus making themselves “extinct”), cancer cells are rapidly evolving population that, by ignoring normal differentiation and regulation, out-compete normal cells for resources and physically disrupt normal tissues. They can mutate at freakishly high rates but remain viable despite highly bizarre genomes. Remember that these are somatic mutations. A small proportion of human cancers arise from germ cell progenitors, or at least show germ-cell like differentiation, but these are all somatic mutations that die out with the cancer clone.

Only a very few cancers have been able to find a way to survive the demise their host/progenitor. Most of these ways require(d) human intervention, either deliberate, like with the HeLa cell line, or mouse sarcoma cells for anti-cancer research, or accidental, like the sad case of a man dying of ovarian cancer after having received a kidney transplant from a woman who had also died of ovarian cancer.

The only cancer that has, thus far, not required human intervention to spread to a new host is the (Tasmanian) Devil Facial Tumor Disease, which is spread by an afflicted Tasmanian devil biting the face/head of another devil.

apokryltaros said: … or accidental, like the sad case of a man dying of ovarian cancer after having received a kidney transplant from a woman who had also died of ovarian cancer.

OK, that one I’ve got to go look up.

Wikipedia lists three naturally-occurring transmissible cancers. In addition to the Devil facial tumor disease, there’s also Canine transmissible venereal tumor, and one that affects Syrian Hamsters and is transmitted by mosquito.

http://en.wikipedia.org/wiki/Clonal[…]sible_cancer

Of course it has been kicked around for a while that head and neck cancer might be contracted from the HPV during cunnilingus.…

Mark Sturtevant said: Of course it has been kicked around for a while that head and neck cancer might be contracted from the HPV during cunnilingus.…

Well, of course that is not transmission of cancer cells!

apokryltaros said:

harold said:

Reed A. Cartwright said:

Yes, you could create mutations artificially, but we are interested in the natural distribution and rate of mutations. Some of our preliminary results indicate that ciliates have really low mutation rates, maybe 10 or more times lower than humans.

Eventually, I’ll unsticky the contest page and put a link to this page in its place.

That is exceedingly interesting. Is that the net mutation rate, after repair mechanisms, or do they seem to have a lower initial rate?

The macronucleus behavior is at least superficially reminiscent of what happens in some, not all but some, human cancer clones, via somatic mutation. Human cancer is a tragic example of evolution at the cellular level (I’ve been saying this for years and now the editors of the New England Journal of Medicine are saying it, too). Although they kill the host eventually if untreated (thus making themselves “extinct”), cancer cells are rapidly evolving population that, by ignoring normal differentiation and regulation, out-compete normal cells for resources and physically disrupt normal tissues. They can mutate at freakishly high rates but remain viable despite highly bizarre genomes. Remember that these are somatic mutations. A small proportion of human cancers arise from germ cell progenitors, or at least show germ-cell like differentiation, but these are all somatic mutations that die out with the cancer clone.

Only a very few cancers have been able to find a way to survive the demise their host/progenitor. Most of these ways require(d) human intervention, either deliberate, like with the HeLa cell line, or mouse sarcoma cells for anti-cancer research, or accidental, like the sad case of a man dying of ovarian cancer after having received a kidney transplant from a woman who had also died of ovarian cancer.

The only cancer that has, thus far, not required human intervention to spread to a new host is the (Tasmanian) Devil Facial Tumor Disease, which is spread by an afflicted Tasmanian devil biting the face/head of another devil.

Mark Sturtevant said:

Of course it has been kicked around for a while that head and neck cancer might be contracted from the HPV during cunnilingus.…

The comment by apokrylataros is completely correct. Human (and animal) cancers can, in a sense, be modeled as a type of evolution within a given environment that inevitably destroys the environment and sends the evolving population into extinction. The Tasmanian devil example, however, appears to spread by allograft. I am not aware of any other example of this. http://en.wikipedia.org/wiki/Devil_[…]mour_disease Incidentally, some rare benign and malignant human tumors show Schwann cell like differentiation. None of them ever spread by allograft.

Viruses, meanwhile, are risk factors for numerous cancers, as well as benign tumors such as warts. This makes sense, because many types of viruses 1) insert themselves into the host genome at some point, causing somatic mutations (as we all know, for example, there are many left over viral genes in the human genome, some of which are expressed, and some of which are even important in the development of the human placenta, although there are also placental mammals which do not use these appropriated viral genes), and 2) sometimes manipulate regulatory signalling pathways to drive cell proliferation or differentiation for their own advantage. Of course, most viruses that afflict humans do NOT cause cancer, and most cancer does not seem to be associated with viruses. The virus associated with the most individual types of cancer is probably Epstein Barr virus, AKA HHV-4; however, only a very tiny fraction of people exposed to EBV ever get one of the associated cancers.

AltairIV said:

Wikipedia lists three naturally-occurring transmissible cancers. In addition to the Devil facial tumor disease, there’s also Canine transmissible venereal tumor, and one that affects Syrian Hamsters and is transmitted by mosquito.

http://en.wikipedia.org/wiki/Clonal[…]sible_cancer

That’s extremely interesting. I should add that humans allograft cancer cells into lab animals, usually mice, quite often.

Allograft spread of cancer must require some powerful immune evasion mechanism, or an excessively inbred population, or perhaps both. Any normal human or animal immune system will reject any allograft not from, and often even from, a carefully matched donor. That’s why transplanting benign organs is such a hassle. Of course, the same goes for microbes, but microbes have countless generations to experiment.

A comment on the human examples given there. First of all, the disorder formerly known as “malignant fibrous histiocytoma”, now “pleomorphic undifferentiated sarcoma”, is a very rare and poorly understood entity, and, as a diagnosis made by exclusion of better understood types of sarcoma, could be a diverse group. Some cases could very well be related to viruses, for all we know. I suspect that case probably was. Kaposi’s sarcoma is driven by HHV-8, another virus associated with multiple tumor types, all relatively rare and all seen mainly in the context of severe immunosuppression, usually due to HIV.

stevaroni said:

apokryltaros said: … or accidental, like the sad case of a man dying of ovarian cancer after having received a kidney transplant from a woman who had also died of ovarian cancer.

OK, that one I’ve got to go look up.

Pardon, it was uterine cancer, not ovarian.

http://abcnews.go.com/Health/Wellne[…]?id=10679140#.Ub4wGvnVCsY

harold said:

AltairIV said:

Wikipedia lists three naturally-occurring transmissible cancers. In addition to the Devil facial tumor disease, there’s also Canine transmissible venereal tumor, and one that affects Syrian Hamsters and is transmitted by mosquito.

http://en.wikipedia.org/wiki/Clonal[…]sible_cancer

That’s extremely interesting. I should add that humans allograft cancer cells into lab animals, usually mice, quite often.

Allograft spread of cancer must require some powerful immune evasion mechanism, or an excessively inbred population, or perhaps both. Any normal human or animal immune system will reject any allograft not from, and often even from, a carefully matched donor. That’s why transplanting benign organs is such a hassle. Of course, the same goes for microbes, but microbes have countless generations to experiment.

It could be that the Tasmanian devils are somewhat inbred, what the current populations being descended from an island refuge population. It could also be that the DFTD multiplies very fast: those devils that don’t starve to death from the tumors hindering their ability to eat food inevitably die from the tumors metasizing into vital internal organs like the heart or lungs.

As far as I know, conservationists’ failsafe plan is to secure several uncontaminated populations in zoos and in wildlife preserves on the mainland, and sadly, let the wild population in Tasmania die out if nothing more can be done to treat the disease.

harold said:

If I understand correctly, ciliates are a fascinating example of a unicellular organism with both germline and somatic mutations. This is very interesting stuff.

And, hence, why we got funded. We really won’t know anything for sure for several more years, as we have to generate new lines first.

apokryltaros said:

It could be that the Tasmanian devils are somewhat inbred, what the current populations being descended from an island refuge population.

Yes, this is the problem with Tasmanian devils. Their genetic diversity is so low that the cancer cells are not recognized as external, which allows them to grow tumors in another individual.

This seems like the perfect system to study mutation rates and distribution of different types of mutations. It should be possible to demonstrate that mutations occur randomly with respect to the needs of the organism, without the confounding effects of selection obscuring the pattern. Is this type of analysis planned as part of the study? Good luck Reed, the project sounds fascinating.

So, one might imagine that the low rate of mutations in ciliates might imply that more mutations result around transcription (exposure to mutagens while unpacked) than previously supposed. Or at least I had previously supposed that mutations are primarily due to replication errors. You think?

DS said:

It should be possible to demonstrate that mutations occur randomly with respect to the needs of the organism, without the confounding effects of selection obscuring the pattern. Is this type of analysis planned as part of the study?

Showing that mutations occur randomly with respect to the needs of the organisms would require us to run a selection experiment. And I’m pretty sure that in this system if we stress the cells, they will reproduce sexually, which we don’t want.

John Harshman said:

So, one might imagine that the low rate of mutations in ciliates might imply that more mutations result around transcription (exposure to mutagens while unpacked) than previously supposed. Or at least I had previously supposed that mutations are primarily due to replication errors. You think?

I’m not sure what the relative contribution is of replication errors versus other types of mutations. We know that spontaneous events have an important function due to the increase in mutation rate of CpG islands that shows up in species-species comparisons.

As far as ciliates, if we confirm the rate, then the first thing that I am going to look at is the replication and repair machinery to determine if there is anything novel with them.

Reed A. Cartwright said:

Yes, this is the problem with Tasmanian devils. Their genetic diversity is so low that the cancer cells are not recognized as external, which allows them to grow tumors in another individual.

What about the canine tumors then? I don’t think anyone would say canids lack genetic diversity. CTVT has been shown to infect a range of species, including foxes and coyotes.

AltairIV said:

Wikipedia lists three naturally-occurring transmissible cancers. In addition to the Devil facial tumor disease, there’s also Canine transmissible venereal tumor, and one that affects Syrian Hamsters and is transmitted by mosquito.

http://en.wikipedia.org/wiki/Clonal[…]sible_cancer

What about HeLa or the Tasmanian Devils?

KlausH said:

AltairIV said:

Wikipedia lists three naturally-occurring transmissible cancers. In addition to the Devil facial tumor disease, there’s also Canine transmissible venereal tumor, and one that affects Syrian Hamsters and is transmitted by mosquito.

http://en.wikipedia.org/wiki/Clonal[…]sible_cancer

What about HeLa or the Tasmanian Devils?

Oops, sorry, I overlooked the Devil listing because of the omission of “Tasmanian”.

AltairIV said:

Reed A. Cartwright said:

Yes, this is the problem with Tasmanian devils. Their genetic diversity is so low that the cancer cells are not recognized as external, which allows them to grow tumors in another individual.

What about the canine tumors then? I don’t think anyone would say canids lack genetic diversity. CTVT has been shown to infect a range of species, including foxes and coyotes.

It sounds as if the immune evasion mechanisms of this entity would be worth studying.

If it only affects canines, and a model can’t be generated in easier to study organisms, that might be a road block.

Reed A. Cartwright said:

DS said:

It should be possible to demonstrate that mutations occur randomly with respect to the needs of the organism, without the confounding effects of selection obscuring the pattern. Is this type of analysis planned as part of the study?

Showing that mutations occur randomly with respect to the needs of the organisms would require us to run a selection experiment. And I’m pretty sure that in this system if we stress the cells, they will reproduce sexually, which we don’t want.

Not necessarily. For example, you could determine the number of synonomous versus non synonomous substitutions, third codon position substitutions versus first and second position, coding versus non coding substitutions, regulatory region substitutions versus non regulatory, substitutions in constitutively expressed genes versus highly regulated genes, substitution in central metabolic genes versus other types of genes, etc. And of course you could also perform the same type of analysis on insertion and deletion mutations. And you could do all of this prior to selection and even possibly after selection as a comparison.

I know, easy for me to say, if I’m not the one doing all the work.

One potentially final comment here.

Multicellularity is a fascinating issue in biology.

Among many other things, more or less by definition, cancer is a disorder of only multicellular organisms.

I have often wondered whether there is a “simplest model of animal cancer” - a very simple organism with definable tissues and a definable, finitely living individuals, which can be afflicted with unequivocal neoplastic disease.

Ciliates seem to be unicellular yet have seperate somatic and germline genetics. Could they have evolved from multicellular ancestors? Represent a current model of a step on the road to multicellularity? Or is this remarkable existence of separate somatic and germline genetics, in a unicellular organism, a coincidence unrelated to multicellularity?

hmm… Has anyone ever seen a Post-Doc advertisement for an ID position?

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This page contains a single entry by Reed A. Cartwright published on June 14, 2013 6:42 PM.

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