Unwinding snail chirality
Applications are invited for a postdoctoral research fellow to work on a three-year project, funded by the BBSRC, on "Unwinding snail chirality".
Although multiple lines of enquiry remain, a deep-seated theoretical problem has stoked a burning interest in understanding the symmetry-breaking event during development - how is one side of an organism consistently distinguished from the other, given that the side that is called 'right' is essentially arbitrary? Although most prior research has concentrated on models such as the mouse, chick and frog, we believe that the pond Lymnaea may be a crucial organism in coming to understand asymmetry, because their chirality is determined very early in development.
The objective of this project is to take advantage of the latest advances in DNA sequencing technology to clone and characterize the determinant of chirality in snails, by a novel method that we term "massive subtractive linkage analysis" (MSLA). A parallel PDRA in Professor Mark Blaxter's lab at the University of Edinburgh (to be advertised separately) will lead the bioinformatic analyses, and there will also be collaboration with David Lambert's lab in Rochester, New York.
Candidates must possess a PhD in molecular genetics or equivalent qualification in a related discipline. Experience of working with RNA and cDNA libraries is essential, as is a meticulous approach to lab work and note-keeping. Experience of high-precision PCR work, genotyping, and micromanipulation of embryos (e.g. microinjection) would also be highly desirable.
Salary range £25888 - £33780 per annum, depending on qualifications and experience (salary can progress to £36912 per annum subject to performance). This post is funded by the BBSRC for a fixed-term of three years, with a provisional start date of October 1st, but with flexibility on the precise start date.
Informal enquiries are encouraged and should be addressed to Dr. Angus Davison, tel: 0115 823 0322 Email: angus.davison@nott.ac.uk, or Dr. Aziz Aboobaker Email: aziz.aboobaker@nott.ac.uk. For the bioinformatic post, a separate enquiry should be made to Prof. Mark Blaxter Email mark.blaxter@ed.ac.uk
Additional information on Dr. Davison's research is available at http://www.nottingham.ac.uk/biology/contacts/davison/research.php
Additional information on Prof. Blaxter's research is available at http://www.nematodes.org/
To formally apply, candidates for the University of Nottingham position should apply on-line (http://jobs.nottingham.ac.uk/) or send a detailed CV and covering letter, together with the names and addresses of two referees, to Dr A Davison, School of Biology, The University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH. Note: we are still waiting for a job reference code and the details are not yet on the University website.
Closing date: Friday 22nd August.
Additional information
For an organism to become asymmetric, bilateral symmetry must somehow be broken during development. Although multiple lines of enquiry remain, a deep-seated theoretical problem has stoked a burning interest in understanding the symmetry-breaking event - how is one side of an organism consistently distinguished from the other, given that the side that is called 'right' is essentially arbitrary? In the hypothetical view of Brown and Wolpert, the solution is provided by a pre-existing asymmetric molecular reference: an asymmetric gradient is created if an 'F-molecule' aligns with anterior-posterior and dorsal-ventral axes, so transporting an effector molecule towards the left or right. Asymmetry is thus entirely dependent upon the chirality (and subsequent alignment) of the F-molecule.
To attempt to validate the hypothesis, attention has focussed on the mouse, chick and zebrafish. In these model organisms, it has been found that rotational beating of cilia in the early gastrula creates an asymmetric extracellular fluid movement. It has therefore been argued that this is the symmetry-breaking step - the chirality of cilial motor proteins leads to directional fluid movement, ultimately determining the molecular and morphological asymmetry.
The unfortunate problem, however, is that a body of research indicates that the symmetry-breaking event sometimes occurs much earlier and at the intracellular level, preceding the commencement of ciliary movement. Together, the results suggest that in invertebrates and at least some vertebrates, molecular asymmetry is established early in embryogenesis, with morphological asymmetry only becoming apparent later. In consequence, the field of left-right patterning is "in disarray", because the notion that the rotary movement of cilia determine asymmetry is an elegant hypothesis that is undermined by earlier symmetry breaking events, even in some vertebrates. If the rotational beating of cilia is the symmetry-breaking step in the mouse, then it is probably the exception.
We therefore intend to develop the pond snail Lymnaea stagnalis as a lab animal to help understand the symmetry-breaking step, following years of neglect. The primary motivation for using Lymnaea is that molluscan asymmetry is established very early, and is genetically tractable; other "genome-era" molluscs do not vary in their chirality and so are of no direct use to this project.
The specific aim of this project is to utilise the power of ultrahigh-throughput DNA sequencing to directly clone the gene for chirality in Lymnaea stagnalis, working on the hypothesis that the maternal determinant of chirality in snail eggs is a molluscan F-molecule, or at least a molecule that interacts with it. With false positives excluded by genetic mapping, we will then attempt to definitively identify the gene with functional and cytological studies.
The general, long-term aim is put in place techniques that will in the future enable a precise understanding of the symmetry-breaking event in snails, stimulating investigative analyses of the same or related molecules in other organisms, including vertebrates. The work is timely because very recent technological advances have made identification of the asymmetry-determining locus feasible within the scale of a three year grant. Much of the work will be outsourced (e.g. sequencing, genotyping)
To ensure an efficient working relationship between the PDRA and the bioinformatician, regular meetings are planned between the Nottingham and Edinburgh groups. The latter will also mount the processed sequences on a publicly accessible database, similar to those already created for EST projects by co-I Blaxter. The PDRA will then use this to mine any further information (e.g. extract contigs); other scientists, may also access the database for their own purposes
--
Mention www.thesciencejobs.com, while you apply
Applications are invited for a postdoctoral research fellow to work on a three-year project, funded by the BBSRC, on "Unwinding snail chirality".
Although multiple lines of enquiry remain, a deep-seated theoretical problem has stoked a burning interest in understanding the symmetry-breaking event during development - how is one side of an organism consistently distinguished from the other, given that the side that is called 'right' is essentially arbitrary? Although most prior research has concentrated on models such as the mouse, chick and frog, we believe that the pond Lymnaea may be a crucial organism in coming to understand asymmetry, because their chirality is determined very early in development.
The objective of this project is to take advantage of the latest advances in DNA sequencing technology to clone and characterize the determinant of chirality in snails, by a novel method that we term "massive subtractive linkage analysis" (MSLA). A parallel PDRA in Professor Mark Blaxter's lab at the University of Edinburgh (to be advertised separately) will lead the bioinformatic analyses, and there will also be collaboration with David Lambert's lab in Rochester, New York.
Candidates must possess a PhD in molecular genetics or equivalent qualification in a related discipline. Experience of working with RNA and cDNA libraries is essential, as is a meticulous approach to lab work and note-keeping. Experience of high-precision PCR work, genotyping, and micromanipulation of embryos (e.g. microinjection) would also be highly desirable.
Salary range £25888 - £33780 per annum, depending on qualifications and experience (salary can progress to £36912 per annum subject to performance). This post is funded by the BBSRC for a fixed-term of three years, with a provisional start date of October 1st, but with flexibility on the precise start date.
Informal enquiries are encouraged and should be addressed to Dr. Angus Davison, tel: 0115 823 0322 Email: angus.davison@nott.ac.uk, or Dr. Aziz Aboobaker Email: aziz.aboobaker@nott.ac.uk. For the bioinformatic post, a separate enquiry should be made to Prof. Mark Blaxter Email mark.blaxter@ed.ac.uk
Additional information on Dr. Davison's research is available at http://www.nottingham.ac.uk/biology/contacts/davison/research.php
Additional information on Prof. Blaxter's research is available at http://www.nematodes.org/
To formally apply, candidates for the University of Nottingham position should apply on-line (http://jobs.nottingham.ac.uk/) or send a detailed CV and covering letter, together with the names and addresses of two referees, to Dr A Davison, School of Biology, The University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH. Note: we are still waiting for a job reference code and the details are not yet on the University website.
Closing date: Friday 22nd August.
Additional information
For an organism to become asymmetric, bilateral symmetry must somehow be broken during development. Although multiple lines of enquiry remain, a deep-seated theoretical problem has stoked a burning interest in understanding the symmetry-breaking event - how is one side of an organism consistently distinguished from the other, given that the side that is called 'right' is essentially arbitrary? In the hypothetical view of Brown and Wolpert, the solution is provided by a pre-existing asymmetric molecular reference: an asymmetric gradient is created if an 'F-molecule' aligns with anterior-posterior and dorsal-ventral axes, so transporting an effector molecule towards the left or right. Asymmetry is thus entirely dependent upon the chirality (and subsequent alignment) of the F-molecule.
To attempt to validate the hypothesis, attention has focussed on the mouse, chick and zebrafish. In these model organisms, it has been found that rotational beating of cilia in the early gastrula creates an asymmetric extracellular fluid movement. It has therefore been argued that this is the symmetry-breaking step - the chirality of cilial motor proteins leads to directional fluid movement, ultimately determining the molecular and morphological asymmetry.
The unfortunate problem, however, is that a body of research indicates that the symmetry-breaking event sometimes occurs much earlier and at the intracellular level, preceding the commencement of ciliary movement. Together, the results suggest that in invertebrates and at least some vertebrates, molecular asymmetry is established early in embryogenesis, with morphological asymmetry only becoming apparent later. In consequence, the field of left-right patterning is "in disarray", because the notion that the rotary movement of cilia determine asymmetry is an elegant hypothesis that is undermined by earlier symmetry breaking events, even in some vertebrates. If the rotational beating of cilia is the symmetry-breaking step in the mouse, then it is probably the exception.
We therefore intend to develop the pond snail Lymnaea stagnalis as a lab animal to help understand the symmetry-breaking step, following years of neglect. The primary motivation for using Lymnaea is that molluscan asymmetry is established very early, and is genetically tractable; other "genome-era" molluscs do not vary in their chirality and so are of no direct use to this project.
The specific aim of this project is to utilise the power of ultrahigh-throughput DNA sequencing to directly clone the gene for chirality in Lymnaea stagnalis, working on the hypothesis that the maternal determinant of chirality in snail eggs is a molluscan F-molecule, or at least a molecule that interacts with it. With false positives excluded by genetic mapping, we will then attempt to definitively identify the gene with functional and cytological studies.
The general, long-term aim is put in place techniques that will in the future enable a precise understanding of the symmetry-breaking event in snails, stimulating investigative analyses of the same or related molecules in other organisms, including vertebrates. The work is timely because very recent technological advances have made identification of the asymmetry-determining locus feasible within the scale of a three year grant. Much of the work will be outsourced (e.g. sequencing, genotyping)
To ensure an efficient working relationship between the PDRA and the bioinformatician, regular meetings are planned between the Nottingham and Edinburgh groups. The latter will also mount the processed sequences on a publicly accessible database, similar to those already created for EST projects by co-I Blaxter. The PDRA will then use this to mine any further information (e.g. extract contigs); other scientists, may also access the database for their own purposes
--
Mention www.thesciencejobs.com, while you apply
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