Neuropeptide function in a decentralised nervous system

Lead Research Organisation: Queen Mary, University of London
Department Name: Sch of Biological and Chemical Sciences

Abstract

Neuropeptides are "messenger molecules" that enable nervous systems to co-ordinate physiological processes and behaviour in humans and other animals. Research on neuropeptides has provided important insights on the molecular basis of the physiological mechanisms that underlie how we feel and behave. For example, we know that morphine exerts its pain-relieving effect in humans because it mimics the action of endogenous neuropeptides - the "endorphins". Whilst discovery of the actions of the neuropeptide oxytocin in neural mechanisms of social behaviour in humans and other animals have led to it being labeled as the "hormone for love and trust". But when did these key molecular regulators of behaviour originate in the evolutionary history of animal life on earth? Answering this question has proven to be difficult because neuropeptides are comprised of only short strings of amino acids. Thus, when comparing neuropeptides in humans with those present in, for example, a distantly related "model" invertebrate such as the fruit fly Drosophila, identifying of relationships between neuropeptides is challenging because of amino acid sequence divergence. However, with the falling cost of DNA sequencing it has become feasible to identify neuropeptide-encoding genes in an increasingly wide range of animals, and this has provided important new insights on the evolutionary history of neuropeptide signaling systems. In particular, it has been the availability of DNA sequence data from a variety of marine invertebrates that has provided critical "missing pieces" in the "jigsaw puzzle" of neuropeptide evolution. For example, the hormone thyrotropin-releasing hormone (TRH), which has a key role in regulating growth in humans, was until recently thought to occur only in vertebrates. But our research has revealed that TRH-type neuropeptides also occur in echinoderms (e.g. sea urchins, starfish), demonstrating that TRH has a much more ancient evolutionary history than hitherto thought.

The aim of this project is to investigate and determine the physiological/behavioural roles of neuropeptides in the common European starfish Asterias rubens. Why this species and why now? Firstly, as an echinoderm, this species belongs to the same branch of the animal kingdom (deuterostomes) as vertebrates and therefore it provides a "missing link" between the well-characterised neuropeptide systems of vertebrates and protostomian invertebrates such as Drosophila. Secondly, starfish and other echinoderms have a pentaradial body plan without a brain (a "decentralized" nervous system), providing a unique context in which to determine how neuropeptide systems are used to control physiological/behavioural processes. Thirdly, Asterias rubens is a very abundant species in European waters, which makes it easy to obtain for experimental studies. Fourthly, using new DNA sequencing technology, we have recently determined the sequences of ~16,000 genes that are expressed in the nervous system of this species, including many neuropeptide genes. Thus, we are now for the first time able to comprehensively investigate neuropeptide function in this echinoderm species. By investigating neuropeptide expression and action in Asterias rubens using a range of techniques (see Technical Summary), we will i). discover the physiological roles of neuropeptides in starfish, providing for the first time comprehensive insights on how neuropeptide systems are used to regulate physiological processes and behaviour in echinoderms, pentaradially symmetrical animals that have a decentralized nervous system without a brain ii). determine to what extent there has been conservation/diversification of neuropeptide function in echinoderms, by comparison of our findings with knowledge of neuropeptide function in other animals (vertebrates and other invertebrates).

Technical Summary

This will be the first multi-gene analysis of neuropeptide expression and function in the nervous system of an echinoderm. We have used Illumina HiSeq to sequence the neural transcriptome of the starfish Asterias rubens, employing SOAP de novo to assemble ~16,000 contigs (>1000 bp). We have identified over 30 neuropeptide precursors and 8 of these have been selected for analysis in this project based on the following criteria: a). they contain a peptide that is a member of an evolutionarily conserved bilaterian neuropeptide family b). they give rise to only one or two putative neuropeptides These are: 1. a vasopressin/oxytocin-type neuropeptide; 2). a NPS/CCAP-type neuropeptide (NGFFYamide); 3. a GnRH-type neuropeptide; 4. a TRH-type neuropeptide; 5. two CCK/gastrin-type neuropeptides; 6. a luqin-type neuropeptide; 7. an orexin-type neuropeptide and 8. a calcitonin-type neuropeptide.

The molecular structure of the neuropeptides will first be determined by analysis of starfish nerve extracts using nanoflow liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Neuropeptide precursor mRNA expression patterns in A. rubens will then be determined using in situ hybridization (ISH) methods, employing enzyme-based and/or fluorescent markers to reveal DIG-labelled probes in serial sections of starfish. Specific antibodies to the neuropeptides will be generated and used for immunocytochemical (ICC) visualization of neuropeptides in starfish. Detailed analysis of neuropeptide expression in A. rubens using ISH and ICC will provide a neuroanatomical framework for investigation of the pharmacological actions of the neuropeptides, using in vivo or in vitro assays to test effects of neuropeptides on a). stomach eversion/retraction b). righting behaviour c). muscle activity d). body wall stiffness e). arm autotomy f). gamete release.

Planned Impact

Who might benefit from this research?

1. Academic beneficiaries: (see above)
2. UK expertise: training the next generation of comparative physiologists
3. Aquaculture industry: shellfish food security
4. Ecosystem services: protection of coral reefs

How might they benefit from this research?

UK expertise: training the next generation of comparative physiologists

The UK has a rich tradition of research in comparative physiology and we are at the beginning of a new era where the falling cost of DNA sequencing is enabling any species to have its genome/transcriptome sequenced. This is expanding the range of animal species that can be utilized to gain molecular insights on physiological processes. The Elphick lab provides a unique contribution to UK research in comparative physiology in using echinoderms (in particular starfish) as experimental systems for neuropeptide biology. Elphick established this field of research as a PhD student (1988-1991; funded by SERC, forerunner to BBSRC) and then moved on to other areas of research, focusing on NO signaling and endocannabinoid signaling (supported by BBSRC grants). Next generation transcriptome sequencing has enabled Elphick to return to a field of research that he pioneered over twenty years ago. In the proposed project Elphick will train a PDRA in echinoderm neurobiology, which will contribute toward maintaining UK expertise and research excellence in comparative neurobiology and echinoderm biology. Furthermore, Elphick's outreach project "A five-sided life: the amazing biology of starfish" is designed to inspire sixth-formers to become the next generation of comparative physiologists in the post-genomic era.

Aquaculture industry: shellfish food security
The common European starfish Asterias rubens feeds on bivalve molluscan species that are economically important as foodstuffs - e.g. mussels, clams, scallops. Starfish predation impacts on the productivity of shellfish aquaculture facilities. For example, a recent study assessing the impact of starfish on scallop aquaculture concludes: "methods for reducing scallop predation by sea stars are necessary". In the proposed project we will obtain new insights into neural mechanisms that control the feeding behaviour of starfish. By identifying and characterizing the mechanisms of action of neuropeptides that trigger stomach eversion or retraction in starfish, we will obtain data that may provide a basis for development of novel strategies for chemical control of starfish predation on shellfish. As a step towards this objective, we will investigate nitric oxide synthase inhibitors as small-molecule inhibitors of neuropeptide-mediated stomach eversion in starfish.

Ecosystem services: protection of coral reefs
The environmental impact of starfish predation is perhaps most infamously associated with the crown-of-thorns-starfish (COTS) Acanthaster plancii, which feeds on coral, causing destruction of the Great Barrier Reef in Australia. Efforts to develop novel strategies to control COTS are focusing on the ongoing sequencing of the genome/transcriptome of Acanthaster plancii, led by Dr Mike Hall at the Australian Institute for Marine Sciences. Recognising that our research on neuropeptidergic control of feeding behaviour in the European starfish Asterias rubens has potential translational relevance to control of COTS, we have established contact with Dr Hall. In this project, we will utilize our Asterias rubens sequence data to identify orthologous neuropeptides in COTS. Informed by experimental findings from this project, we will then seek to secure funding to establish a collaborative project with Dr Hall's group that would directly investigate the actions of neuropeptides on the feeding behaviour of COTS. This may then provide a basis for development of novel methods for chemical control of COTS, with concomitant potential benefits to coral reefs as ecosystem services.

Publications

10 25 50
 
Description The project has provided important new insights into the evolution and comparative physiology of neuropeptide signalling systems.

1. Evolution of neuropeptide signalling

Prior to this project, our knowledge of the evolution of neuropeptide signalling systems was largely based on findings from studies on vertebrates and "model" protostomian invertebrates (e.g. Drosophila). What were missing were insights from deuterostomian invertebrates (e.g. echinoderms such as the starfish Asterias rubens) that occupy an "intermediate" evolutionary position with respect to vertebrates and protostomes. By characterising neuropeptide signalling in A. rubens we have obtained important new insights into neuropeptide evolution. For example, prior to this project it was thought that the neuropeptide corazonin only occurs in protostomes. Our discovery of corazonin-type signalling in starfish has revealed that corazonin signalling is also present in deuterostomian invertebrates but has been lost in vertebrates (see BBSRC website: https://bbsrc.ukri.org/news/fundamental-bioscience/2016/160628-pr-lost-hormone-found-in-starfish/). We have also published review articles that discuss how our findings from starfish have contributed to knowledge of neuropeptide evolution in the animal kingdom (e.g. Elphick et al., 2018, J. Exp. Biol.).

2. Neuropeptide function

The evolutuionary origin of a least thirty neuropeptide signalling systems has been traced back to the common ancestor of bilaterian animals. However, the functional significance of the huge diversity of neuropeptides that occur in animals remains poorly understood. To obtain new insights into the evolution of neuropeptide function in the animal kingdom, we carried out the first extensive analysis of neuropeptide expression in an echinoderm. A notable finding was that at least twenty types of neuropeptides are expressed in the starfish stomach. This was of interest because feeding in starfish is dynamic process where the stomach is everted out of the mouth over prey (e.g. mussels) and then when feeding is completed the stomach is retracted. By investigating the effects of neuropeptides on the starfish stomach, we have discovered that multiple neuropeptides are involved in regulation of stomach eversion or retraction. For example, an oxytocin-type neuropeptide induces stomach eversion and a feeding posture. Conversely, the neuropeptides ArCCK and NGFFYamide trigger stomach retraction and inhibit feeding behaviour. These are important findings because they provide new insights into the evolution of neuropeptide function in the animal kingdom and the physiology of starfish feeding behaviour. We have also obtained new insights into how neuropeptides regulate reproduction in starfish by identifying cells located at the tips of the arms that produce a hormone (RGP) that triggers release of eggs or sperm.

3. Functional anatomy of the starfish nervous system.

Starfish and other echinoderms are remarkable animals because they exhibit pentaradial symmetry and, unlike their bilaterally symmetrical ancestors, do not have a head / brain. Using antibodies to a variety of different neuropeptides, we have revealed features of the starfish nervous system that have never been seen before. For example, we have revealed for the first time the anatomy of peptidergic neurons that innervate skeletal muscles located in body wall of starfish.
Exploitation Route Our research on neuropeptide signalling in the common European starfish A. rubens has had impact on the work of other researchers and provided a basis for potential applications. For example:

1. Informed by our findings from starfish, we have proposed a new system of nomenclature for GnRH/corazonin-type neuropeptides (Zandawala et al., 2018; Gen. Comp. Endocrinol; 21 citations thus far). This has had and will have impact in influencing interpretation of research findings in the field of comparative endocrinology.

2. Our disovery of starfish GnRH has enabled identification of a high-affinity copper-binding site in GnRH-type peptides (Tran et al., 2019; Metallomics), which may be useful for development of novel and potent analogues of human GnRH that could be used clinically in reproductive medicine.

3. Our research on A. rubens has informed the research of scientists based in Australia that are investigating novel approaches for control of a pest starfish species, Acanthaster planci, which feeds on coral. In particular, our discovery of neuropeptides that regulate feeding behaviour in starfish may provide basis for novel control methods. To enable further investigation of this we are working in collaboration with Dr Scott Cummins (University of the Sunshine Coast, Australia) to investigate the effects of neuropeptides on feeding in A. planci; this work is supported by a grant that was recently awarded by the Leverhulme Trust (RPG-2018-200).
Sectors Aerospace, Defence and Marine,Agriculture, Food and Drink,Education,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://www.researchpublications.qmul.ac.uk/publications/staff/21463.html
 
Description Daiwa Foundation Small Grant
Amount £2,000 (GBP)
Funding ID 9737/13393 
Organisation Daiwa Foundation Small Grants 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2019 
End 05/2019
 
Description EMBO short-term fellowship
Amount £10,000 (GBP)
Funding ID ASTF 168-2014 
Organisation European Molecular Biology Organisation 
Sector Learned Society
Country European Union (EU)
Start 01/2015 
End 04/2015
 
Description Leverhulme Trust Project Grant
Amount £213,916 (GBP)
Funding ID RPG-2018-200 
Organisation The Leverhulme Trust 
Sector Academic/University
Country United Kingdom
Start 09/2018 
End 08/2021
 
Description Leverhulme Trust Project Grant
Amount £113,015 (GBP)
Funding ID RPG-2016-353 
Organisation The Leverhulme Trust 
Sector Academic/University
Country United Kingdom
Start 04/2017 
End 03/2019
 
Description Studentship awarded to Nayeli Escudero Castelan for a 4 year PhD under my supervision at QMUL
Amount £48,000 (GBP)
Organisation National Council on Science and Technology (CONACYT) 
Sector Public
Country Mexico
Start 01/2018 
End 12/2021
 
Description Studentship awarded to Ya Zhang for a 4 year PhD under my supervision at QMUL
Amount £52,800 (GBP)
Organisation University of Leeds 
Department China Scholarship Council
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 08/2020
 
Title Development of rabbit antibodies to a starfish TRH-type neuropeptide 
Description Rabbit antibodies to a starfish TRH-type neuropeptide have been generated and affinity purified. Immunocytochemical analysis of sections of the starfish species Asterias rubens indicates that these antibodies can be used to visualise expression of TRH-type peptides in starfish. 
Type Of Material Antibody 
Provided To Others? No  
Impact none yet 
 
Title Development of rabbit antibodies to the starfish CCK-type neuropeptide ArCCK1 
Description Rabbit antibodies to the starfish CCK-type neuropeptide ArCCK1 have been generated and affinity purified. Immunocytochemical analysis of sections of the starfish species Asterias rubens indicates that these antibodies can be used to visualise expression of ArCCK1 in starfish. 
Type Of Material Antibody 
Provided To Others? No  
Impact none yet 
 
Title Development of rabbit antibodies to the starfish GnRH-type neuropeptide ArGnRH 
Description Rabbit antibodies to the starfish GnRH-type neuropeptide ArGnRH have been generated and affinity purified. Immunocytochemical analysis of sections of the starfish species Asterias rubens indicates that these antibodies can be used to visualise expression of ArGnRH in starfish. 
Type Of Material Antibody 
Year Produced 2017 
Provided To Others? Yes  
Impact A paper reporting the expression of ArGnRH in Asterias rubens that utilised the antibodies to ArGnRH was published in Frontiers in Endocrinology in 2017 (see below for URL and DOI) 
URL https://www.frontiersin.org/articles/10.3389/fendo.2017.00259/full
 
Title Development of rabbit antibodies to the starfish calcitonin-type neuropeptide ArCT 
Description Rabbit antibodies to the starfish calcitonin-type neuropeptide ArCT have been generated. Immunocytochemical analysis of sections of the starfish species Asterias rubens revealed that these antibodies can be used to visualise expression of ArCT. 
Type Of Material Antibody 
Year Produced 2018 
Provided To Others? Yes  
Impact A paper reporting the use of these antibodies for immunohistochemical analysis of ArCT expression in Asterias rubens titled "Biochemical, Anatomical, and Pharmacological Characterization of Calcitonin-Type Neuropeptides in Starfish: Discovery of an Ancient Role as Muscle Relaxants" has been published in Frontiers in Neuroscience (see below). 
URL https://www.frontiersin.org/articles/10.3389/fnins.2018.00382/full
 
Title Development of rabbit antibodies to the starfish neuropeptide ArPPLN1b 
Description Rabbit antibodies to the starfish pedal peptide/orcokinin-type neuropeptide ArPPLN1b wwre generated. Immunocytochemical analysis of sections of the starfish species Asterias rubens revealed that these antibodies can be used to visualise expression of ArPPLN1b in starfish. 
Type Of Material Antibody 
Year Produced 2017 
Provided To Others? Yes  
Impact This antibody enabled the first immunohistochemical analysis of the expression of a pedal peptide/orcokinin-type neuropeptide in an echinoderm (Lin et al., 2017; https://onlinelibrary.wiley.com/doi/full/10.1002/cne.24309). 
URL https://onlinelibrary.wiley.com/doi/full/10.1002/cne.24309
 
Title Development of rabbit antibodies to the starfish neuropeptide ArPPLN2h 
Description Rabbit antibodies to the starfish pedal peptide/orcokinin-type neuropeptide ArPPLN2h wwre generated. Immunocytochemical analysis of sections of the starfish species Asterias rubens revealed that these antibodies can be used to visualise expression of ArPPLN2h in starfish. 
Type Of Material Antibody 
Year Produced 2018 
Provided To Others? Yes  
Impact This antibody enabled the immunohistochemical analysis of the expression of the pedal peptide/orcokinin-type neuropeptide ArPPLN2h in the starfish Asterias rubens (Lin et al., 2018; https://onlinelibrary.wiley.com/doi/full/10.1002/cne.24371). 
URL https://onlinelibrary.wiley.com/doi/full/10.1002/cne.24371
 
Title Development of rabbit antibodies to the starfish orexin-type neuropeptide ArOX1 
Description Rabbit antibodies to the starfish orexin-type neuropeptide ArOX1 have been generated and affinity purified. Immunocytochemical analysis of sections of the starfish species Asterias rubens indicates that these antibodies can be used to visualise expression of ArOX1 in starfish. 
Type Of Material Antibody 
Year Produced 2017 
Provided To Others? No  
Impact None yet 
 
Title Development of rabbit antibodies to the starfish orexin-type neuropeptide ArOX2 
Description Rabbit antibodies to the starfish orexin-type neuropeptide ArOX2 have been generated and affinity purified. Immunocytochemical analysis of sections of the starfish species Asterias rubens indicates that these antibodies can be used to visualise expression of ArOX2 in starfish. 
Type Of Material Antibody 
Year Produced 2017 
Provided To Others? No  
Impact None yet 
 
Title Development of rabbit antibodies to the starfish vasopressin/oxytocin-type neuropeptide "asterotocin" 
Description Rabbit antibodies to starfish vasopressin/oxytocin-type neuropeptide "asterotocin" have been generated and affinity purified. Immunocytochemical analysis of sections of the starfish species Asterias rubens indicates that these antibodies can be used to visualise expression of asterotocin in starfish. 
Type Of Material Antibody 
Provided To Others? No  
Impact Our initial research findings using these antibodies were presented at the 2015 annual meeting of the Society for Experimental Biology in Prague. http://www.sebiology.org/meetings/Past_Meetings/Prague2015/programmes/Programme_Thursday2ndJuly.pdf 
 
Description Characterisation of calcitonin-type neuropeptides in starfish 
Organisation Pukyong National University
PI Contribution Calcitonin (CT) is a peptide hormone released by the thyroid gland that regulates blood Ca2+ levels in mammals. The CT gene is alternatively spliced, with one transcript encoding CT and another transcript encoding the CT-like neuropeptide calcitonin-gene related peptide (a-CGRP), which is a powerful vasodilator. Other CT-related peptides in vertebrates include adrenomedullin, amylin, and intermedin, which also act as smooth muscle relaxants. The evolutionary origin of CT-type peptides has been traced to the bilaterian common ancestor of protostomes and deuterostomes and a CT-like peptide (DH31) has been identified as a diuretic hormone in some insect species. However, little is known about the physiological roles of CT-type peptides in other invertebrates. We characterized a CT-type neuropeptide in a deuterostomian invertebrate-the starfish Asterias rubens (Phylum Echinodermata). A CT-type precursor cDNA (ArCTP) was sequenced and the predicted structure of the peptide (ArCT) derived from ArCTP was confirmed using mass spectrometry. The distribution of ArCTP mRNA and the ArCT peptide was investigated using in situ hybridization and immunohistochemistry, respectively, revealing stained cells/processes in the nervous system, digestive system, and muscular organs, including the apical muscle and tube feet. Investigation of the effects of synthetic ArCT on in vitro preparations of the apical muscle and tube feet revealed that it acts as a relaxant, causing dose-dependent reversal of acetylcholine-induced contraction. Combined with the findings of our collaborator Dr Nam Gyu Park (see below), our findings indicate that the physiological action of CT-related peptides as muscle relaxants in vertebrates may reflect an evolutionarily ancient role of CT-type neuropeptides that can be traced back to the common ancestor of deuterostomes.
Collaborator Contribution Dr Nam Gyu Park and his team at Pukyong National University purified a muscle relaxant from an extract of the starfish Patiria pectinifera and discovered that it was a calcitonin-type peptide (PpCT). RT-qPCR revealed that in P. pectinifera the PpCT precursor transcript is more abundant in the radial nerve cords than in other tissues/organs analyzed. By combining findings from both A. rubens and P. pectinifera, independent and complementary lines of research enabled the first functional characterisation of CT-type neuropeptides in an echinoderm. A collaborative paper reporting our findings were published in 2018 (see below).
Impact Cai W, Kim CH, Go HJ, Egertová M, Zampronio CG, Jones AM, Park NG, Elphick MR. (2018) Biochemical, Anatomical, and Pharmacological Characterization of Calcitonin-Type Neuropeptides in Starfish: Discovery of an Ancient Role as Muscle Relaxants. Front Neurosci. 12:382. doi: 10.3389/fnins.2018.00382. https://www.frontiersin.org/articles/10.3389/fnins.2018.00382/full Other publications that have resulted from this collaboration include: Kim CH, Go HJ, Oh HY, Park JB, Lee TK, Seo JK, Elphick MR, Park NG. (2018) Identification of a novel antimicrobial peptide from the sea star Patiria pectinifera. Dev Comp Immunol. 86:203-213. doi: 10.1016/j.dci.2018.05.002. Kim CH, Go HJ, Oh HY, Elphick MR, Park NG. Identification of evolutionarily conserved residues required for the bioactivity of a pedal peptide/orcokinin-type neuropeptide. Peptides. 103:10-18. doi:10.1016/j.peptides.2018.03.007. Kim CH, Go HJ, Oh HY, Jo YH, Elphick MR, Park NG (2017). Transcriptomics reveals tissue/organ-specific differences in gene expression in the starfish Patiria pectinifera. Marine Genomics. S1874-7787(17)30179-4. doi: 10.1016/j.margen.2017.08.011. Kim CH, Kim EJ, Go HJ, Oh HY, Lin M, Elphick MR, Park NG (2016) Identification of a novel starfish neuropeptide that acts as a muscle relaxant. J. Neurochem 137, 33-45. doi: 10.1111/jnc.13543.
Start Year 2015
 
Description Characterisation of copper binding to the starfish GnRH-type neuropeptide ArGnRH 
Organisation Western Sydney University
Country Australia 
Sector Academic/University 
PI Contribution In vertebrates gonadotropin-releasing hormone I (GnRH-I) is a key regulator of reproductive development and function. The receptor-binding activity of human GnRH-I can be modified by the presence of divalent copper. Thus, copper binding to N-terminal amino acids in GnRH-I induces structural changes that influence receptor interactions and downstream intracellular signalling cascades. It is not known if copper-binding is restricted to human GnRH-I or if it is also a feature of GnRH-type peptides that have been identified in other taxa. To investigate this, we worked in collaboration with Dr Chris Jones (Western Sydney University) investigate copper binding a GnRH-type peptide (ArGnRH) from the starfish Asterias rubens (ArGnRH). To enable this we provided Dr Jones with samples of synthetic ArGnRH. Furthermore, I performed a phylogenetic analysis of the sequences of GnRH-type neuropeptides to investigate the evolution of copper-binding sites in these peptides. A paper reporting these findings was published in the journal Metallomics in 2019 (see below for details). We concluded that copper-binding is an evolutionarily ancient feature of GnRH-type peptides that has been retained, modified or lost in different lineages.
Collaborator Contribution Using a range of spectroscopic and biophysical techniques, Dr Jones and his research team discovered that ArGnRH can bind copper(ii) and nickel(ii). Copper(ii) is bound in a square-planar, high-affinity (Kd ~ 10-12 M) site incorporating four nitrogen donor atoms from a histidine imidazole group, two amides and the N-terminal amine group. The ArGnRH copper affinity and geometry are quite different to human GnRH-I.
Impact Tran KK, Jayawardena BM, Elphick MR, Jones CE. (2019) A gonadotropin-releasing hormone type neuropeptide with a high affinity binding site for copper(II) and nickel(II). Metallomics (in press) https://pubs.rsc.org/en/Content/ArticleLanding/2019/MT/C8MT00279G
Start Year 2016
 
Description Characterisation of neuropeptide signalling systems in the crown-of-thorns starfish Acanthaster plancii 
Organisation Australian Government
Department Australian Institute of Marine Science
Country Australia 
Sector Public 
PI Contribution 1. My research team has analysed Acanthaster plancii transcriptome/genome sequence data to identify transcripts/genes encoding neuropeptide precursors 2. My research team has investigated neuropeptide expression in Acanthaster plancii using antibodies that we have generated to neuropeptides from Asterias rubens 3. My research team has provided technical advice to Ciemon Caballes (James Cook University) for a project that will investigate effects of the neuropeptide NGFFYamide on Acanthaster plancii. This project is informed by our publication - Semmens et al (2013); doi: 10.1242/jeb.092171. To accomplish this planned work Ciemon Caballes has applied for a 2016 COTS Research Grant. 4. A PhD student (Meaghan Smith) working in the laboratory of Dr Scott Cummins (University of the Sunshine Coast) will be visiting my laboratory at QMUL during 2017 to investigate neuropeptide expression in Acanthaster plancii, informed by our findings from Asterias rubens.
Collaborator Contribution 1. Dr Mike Hall (AIMS) and Dr Scott Cummins (University of the Sunshine Coast) have provided my research team with access to Acanthaster plancii transcriptome/genome sequence data 2. Dr Mike Hall (AIMS) and Dr Scott Cummins (University of the Sunshine Coast) have provided my research team with fixed specimens of Acanthaster plancii.
Impact A paper reporting findings from our analysis of Acanthaster plancii transcriptome/genome sequence and mass spectrometry data has been published: Smith MK, Wang T, Suwansa-Ard S, Motti CA, Elizur A, Zhao M, Rowe ML, Hall MR, Elphick MR, Cummins SF (2017) The neuropeptidome of the Crown-of-Thorns Starfish, Acanthaster planci. J Proteomics 165:61-68. doi: 10.1016/j.jprot.2017.05.026
Start Year 2013
 
Description Characterisation of neuropeptide signalling systems in the crown-of-thorns starfish Acanthaster plancii 
Organisation James Cook University
Country Australia 
Sector Academic/University 
PI Contribution 1. My research team has analysed Acanthaster plancii transcriptome/genome sequence data to identify transcripts/genes encoding neuropeptide precursors 2. My research team has investigated neuropeptide expression in Acanthaster plancii using antibodies that we have generated to neuropeptides from Asterias rubens 3. My research team has provided technical advice to Ciemon Caballes (James Cook University) for a project that will investigate effects of the neuropeptide NGFFYamide on Acanthaster plancii. This project is informed by our publication - Semmens et al (2013); doi: 10.1242/jeb.092171. To accomplish this planned work Ciemon Caballes has applied for a 2016 COTS Research Grant. 4. A PhD student (Meaghan Smith) working in the laboratory of Dr Scott Cummins (University of the Sunshine Coast) will be visiting my laboratory at QMUL during 2017 to investigate neuropeptide expression in Acanthaster plancii, informed by our findings from Asterias rubens.
Collaborator Contribution 1. Dr Mike Hall (AIMS) and Dr Scott Cummins (University of the Sunshine Coast) have provided my research team with access to Acanthaster plancii transcriptome/genome sequence data 2. Dr Mike Hall (AIMS) and Dr Scott Cummins (University of the Sunshine Coast) have provided my research team with fixed specimens of Acanthaster plancii.
Impact A paper reporting findings from our analysis of Acanthaster plancii transcriptome/genome sequence and mass spectrometry data has been published: Smith MK, Wang T, Suwansa-Ard S, Motti CA, Elizur A, Zhao M, Rowe ML, Hall MR, Elphick MR, Cummins SF (2017) The neuropeptidome of the Crown-of-Thorns Starfish, Acanthaster planci. J Proteomics 165:61-68. doi: 10.1016/j.jprot.2017.05.026
Start Year 2013
 
Description Characterisation of neuropeptide signalling systems in the crown-of-thorns starfish Acanthaster plancii 
Organisation University of the Sunshine Coast
Country Australia 
Sector Academic/University 
PI Contribution 1. My research team has analysed Acanthaster plancii transcriptome/genome sequence data to identify transcripts/genes encoding neuropeptide precursors 2. My research team has investigated neuropeptide expression in Acanthaster plancii using antibodies that we have generated to neuropeptides from Asterias rubens 3. My research team has provided technical advice to Ciemon Caballes (James Cook University) for a project that will investigate effects of the neuropeptide NGFFYamide on Acanthaster plancii. This project is informed by our publication - Semmens et al (2013); doi: 10.1242/jeb.092171. To accomplish this planned work Ciemon Caballes has applied for a 2016 COTS Research Grant. 4. A PhD student (Meaghan Smith) working in the laboratory of Dr Scott Cummins (University of the Sunshine Coast) will be visiting my laboratory at QMUL during 2017 to investigate neuropeptide expression in Acanthaster plancii, informed by our findings from Asterias rubens.
Collaborator Contribution 1. Dr Mike Hall (AIMS) and Dr Scott Cummins (University of the Sunshine Coast) have provided my research team with access to Acanthaster plancii transcriptome/genome sequence data 2. Dr Mike Hall (AIMS) and Dr Scott Cummins (University of the Sunshine Coast) have provided my research team with fixed specimens of Acanthaster plancii.
Impact A paper reporting findings from our analysis of Acanthaster plancii transcriptome/genome sequence and mass spectrometry data has been published: Smith MK, Wang T, Suwansa-Ard S, Motti CA, Elizur A, Zhao M, Rowe ML, Hall MR, Elphick MR, Cummins SF (2017) The neuropeptidome of the Crown-of-Thorns Starfish, Acanthaster planci. J Proteomics 165:61-68. doi: 10.1016/j.jprot.2017.05.026
Start Year 2013
 
Description Localisation of neuropeptide gene expression in larvae of the starfish Asterias rubens 
Organisation Russian Academy of Sciences
Department Koltzov Institute of Developmental Biology
Country Russian Federation 
Sector Academic/University 
PI Contribution My research team has provided the research tools and facilities required to enable Dr Tatiana Mayorova (Koltzov Institute of Developmental Biology RAS) to investigate neuropeptide gene expression in larvae of the starfish Asterias rubens using mRNA in situ hybridisation methods. Dr Mayorova was supported by an EMBO short-term fellowship to conduct this research in my laboratory from January 2015-April 2015.
Collaborator Contribution Dr Tatiana Mayorova (Koltzov Institute of Developmental Biology RAS) investigated neuropeptide gene expression in larvae of the starfish Asterias rubens using mRNA in situ hybridisation methods. Dr Mayorova was supported by an EMBO short-term fellowship to conduct this research in my laboratory from January 2015-April 2015.
Impact Dr Mayorova presented a poster reporting the findings of this study at the 13th Symposium on Invertebrate Neurobiology held on August 26-30, 2015 at Balaton Limnological Institute in Tihany, Hungary. A paper reporting the findings of this study was published in Frontiers in Neuroscience in 2016: http://journal.frontiersin.org/article/10.3389/fnins.2016.00553/full
Start Year 2015
 
Description 25 Genomes Project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact During 2017 I led a successful bid for the genome of the starfish Asterias rubens to be sequenced by the Sanger Institute for its 25 Genomes Project (http://www.sanger.ac.uk/news/view/25-species-revealed-25-genomes-project). 25 Genomes was funded by the Wellcome Trust Sanger Institute as part of their 25th Anniversary celebrations. In 2018, the Institute is going to decode the DNA of 25 UK species for the first time, five of which were decided by the 25 Genomes public vote. I led the team that successfully championed Asterias rubens, with the team including the BBSRC-funded PDRA working on this grant (Dr Ana Tinoco) and other PDRAs and PhD students in my research group at QMUL and colleagues based at the Oxford University Museum (Dr Imran Rahman), Natural History Museum (Dr Tim Ewin), UCL (Dr Paola Oliveri) and the University of Mons (Prof. Patrick Flammang and Dr Jerome Delroisse - former PDRA funded by this grant). Over five weeks we championed Asterias rubens to have its genome sequenced, competing for votes in the Cryptic Zone from school students and the public and answering questions about many aspects of starfish biology and genome sequencing in 23 online Q&A sessions with schools.

Schools all over the UK were involved, as well as schools in Ireland, Europe and the USA. In the Cryptic Zone 418 students took part in 23 Live Chats with the Species Champions, as well as sending 96 questions in the ASK section. Over 3,000 members of the public logged in to have their say and there were nearly 30,000 views of the Cryptic Zone webpage. There were also two drop-in Live Chats open for the public. In total, there were nearly 5,000 votes, with 1127 of these in Cryptic Zone.
Year(s) Of Engagement Activity 2017
URL https://about.imascientist.org.uk/2017/25-genomes-zone-report/
 
Description Press release for paper published in Scientific Reports - "Urbilaterian origin of paralogous GnRH and corazonin neuropeptide signalling pathways" 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact QMUL press release - Lost hormone is found in starfish - Tuesday 28 June 2016 - "Biologists from Queen Mary University of London (QMUL) have discovered that the evolutionary history of a hormone responsible for sexual maturity in humans is written in the genes of the humble starfish." http://www.qmul.ac.uk/media/news/items/se/178410.html

This press release relates to a paper published in Scientific Reports, which is one of the publication outputs of this BBSRC-funded project: http://www.nature.com/articles/srep28788

Evidence of the impact of this press release is an Altmetric score of 75, which ranks the paper in the 97th percentile (ranked 7,437th) of the 252,583 tracked articles of a similar age in all journals.

The press release was picked up and reported on widely; e.g.
https://www.sciencedaily.com/releases/2016/06/160628072037.htm
http://www.sciencenewsline.com/news/2016062818520052.html
http://www.paneuropeannetworks.com/science-technology/researchers-find-missing-hormone/
http://zeenews.india.com/news/eco-news/human-sex-hormone-has-its-evolutionary-evidence-in-starfish_1901262.html

The BBSRC also picked up on the press release and reported it as a news item on the BBSRC website:
http://www.bbsrc.ac.uk/news/fundamental-bioscience/2016/160628-pr-lost-hormone-found-in-starfish/
Year(s) Of Engagement Activity 2016
URL http://www.qmul.ac.uk/media/news/items/se/178410.html
 
Description Press release for publication of Open Biology paper "Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution" 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact QMUL press release - Starfish reveal the origins of brain messenger molecules - Wednesday 10 February 2016

Biologists from Queen Mary University of London (QMUL) have discovered the genes in starfish that encode neuropeptides - a common type of chemical found in human brains. The revelation gives researchers new insights into how neural function evolved in the animal kingdom.

http://www.qmul.ac.uk/media/news/items/se/170569.html

This press release relates to a paper published in Open Biology, which provides the basis for this BBSRC-funded project.
http://rsob.royalsocietypublishing.org/content/6/2/150224

Evidence of the impact of this press release can be found in an Altmetric score of 51 for the paper, which places it in the top 5% of all research outputs scored by Altmetric

The press release was picked up and reported on widely; e.g.
http://www.scienceworldreport.com/articles/37021/20160210/starfish-neurpeptides-help-find-origins-brain-chemicals-found-humans.htm
https://www.sciencedaily.com/releases/2016/02/160209221156.htm
https://phys.org/news/2016-02-starfish-reveal-brain-messenger-molecules.html
Year(s) Of Engagement Activity 2016
URL http://www.qmul.ac.uk/media/news/items/se/170569.html
 
Description Press release for publication of PNAS paper "Interfibrillar stiffening of echinoderm mutable collagenous tissue demonstrated at the nanoscale" 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact QMUL press release - Scientists discover mechanisms of shape-shifting sea cucumbers - 5 October 2016 - Scientists from Queen Mary University of London (QMUL) have discovered for the first time how marine animals called sea cucumbers can rapidly change the stiffness of their body, which could provide a useful basis for developing novel biomaterials for applications in medicine.
http://www.qmul.ac.uk/media/news/items/se/182174.html

This press release relates to a paper published in PNAS.
http://www.pnas.org/content/113/42/E6362.abstract

Evidence of the impact of this press release can found in an Altmetric score of 68 for the paper, which places it in the 96 percentile of a sample of 225378 of the 233567 tracked articles of a similar age in all journals.

The press release was picked by numerous organisations reporting and/or discussing the significance of the findings of this paper, including:

http://www.esrf.eu/home/UsersAndScience/Publications/Highlights/highlights-2016/CBS/CBS02.html
https://academic.oup.com/bioscience/article-abstract/67/3/201/2962463/Biology-and-Light-SourcesSynchrotrons-allow?redirectedFrom=fulltext
http://nanotechweb.org/cws/article/tech/66675
https://phys.org/news/2016-10-scientists-mechanisms-shape-shifting-sea-cucumbers.html
http://thescienceexplorer.com/nature/shape-shifting-sea-cucumbers-inspire-new-biomaterials
http://www.skinmagazine.co.uk/could-the-sea-cucumbers-unique-shape-shifter-collagen-be-the-secret-to-anti-ageing

The press release was also picked up by the BBSRC and featured in:
1. A news item on the BBSRC website:
http://www.bbsrc.ac.uk/news/fundamental-bioscience/2016/161007-pr-scientists-discover-mechanisms-shape-shifting-sea-cucumbers/

2. The BBSRC Chief executive's review of highlights from 2016:
http://www.bbsrc.ac.uk/news/policy/2016/161212-n-seasons-greetings-from-bbsrc/

3. BBSRC Business - Winter 2017 issue:
http://www.bbsrc.ac.uk/news/business-magazine/2017/Winter-2017/
Year(s) Of Engagement Activity 2016
URL http://www.qmul.ac.uk/media/news/items/se/182174.html
 
Description Royal Society meeting on "Evolution and functional biology of neuropeptide signalling: from genomes to behaviour" (March 13-14 2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I co-organised and presented research supported by this grant at a Royal Society meeting on "Evolution and functional biology of neuropeptide signalling: from genomes to behaviour" (March 13-14 2017). This was attended by ~100 researchers from around the world, providing opportunities to discuss current thinking on this field of research. There was extensive discussion of neuropeptide relationships and nomenclature. The event was also attended by PhD students and postdoctoral researchers, including BBSRC-funded postdocs supported by this grant (Dr Jerome Delroisse and Dr Ana Tinoco). Furthermore, three review articles written by meeting participants were published in J. Exp. Biol. in February 2017: http://jeb.biologists.org/content/221/3/jeb151092 (M.R. Elphick, corresponding author) http://jeb.biologists.org/content/221/3/jeb166710 http://jeb.biologists.org/content/221/3/jeb151167
Year(s) Of Engagement Activity 2017
URL https://royalsociety.org/science-events-and-lectures/2017/03/neuropeptide-signalling/