Research and Development

At the Laboratory of Molecular Neuroendocrinology (LMN), we direct our studies towards understanding how crustaceans respond pathophysiologically to parasites and harnessing the acquired knowledge for technological applications in economically valuable species. 

Crustaceans, as a group of arthropods with species adapting to drastically different environments, are characterized as having rich repertoires of signaling factors involved in neural sensing, endocrine signaling, immune regulation etc. (Lai and Aboobaker, 2017; Chen et al., 2020; Polinsk et al., 2021). As the global demand for seafood products is getting more and more relied on supplies from aquaculture industry, in lieu of wild capture fisheries (World Bank Report No. 83177-GLB, 2013), science-based aquaculture applications for better yield, healthier products are vital issues to be addressed. 

Specifically, we characterize the responses of the neuro-endocrine and immune systems of crustacean hosts to various types of parasites, in relation to metabolism, growth, reproduction, and immune defense of the host, using state-of-the-art technology.  





Upper: Pacific white shrimp Lippenaeus vannamei; Middle: The mud crab Scylla olivacea; Lower: Antarctic krill Euphausia superba (photo credit: Dr. Jean-Yves Toullec).  


We demonstrated that pathological release of metabolic hormones from the neuroendocrine tissues of host animal, in response to viral infection, promotes viral replication in host tissues (Lin et al., 2013; Li et al., 2017; 2019); silencing of gene expression of the metabolic hormone significantly decreases tissues’ viral load and prolongs the survival of virus-infected animals. Accordingly, anti-viral treatments for white spot syndrome (WSS) in penaeid shrimp and crayfish are being refined on the basis of preventing, using RNAi-based gene-silencing approaches, pathological neuro-endocrine responses to the infection of WSS virus.  




(Upper) Metabolic roles of crustacean hyperglycemic hormone (CHH) in the tissues. Anti-viral treatments are designed based on blocking excessive metabolic responses invoked by the virus-enhanced CHH release (Lin et al., 2013; Li et al., 2017; 2019). (Lower) Ribbon structure of 2 CHH-superfamily peptides (Tsai et al., 2008; Chang et al., 2010; Liu et al., 2015; Chen et al., 2020). 


A parasite-host system involving the parasitic barnacle (Sacculina plana) parasitizing crustacean hosts is being extensively studied for understanding the mechanism of control of the host. Many aspects of the host, including immunity, reproduction, molting (growth), sex determination, etc., are controlled by the parasite. Harnessing the knowledge advanced in these fronts, we are characterizing the controlling factors that are involved in regulating molting, reproduction, sex differentiation, and immune functions and applying these factors to aquaculture of commercially important species.  

The parasite’s female larva infests its host by developing into a tissue-infiltrating internal root system (the interna) for nutrient absorption and control of host (Hsiao et al., 2015; Miroliubov et al., 2020). A central cluster of cells later develops into the female reproductive organ (the externa), which emerges on the ventral side of the host’s abdomen. 


(Left) A tissue section showing infiltrating roots (R) of the interna in the ovary of a parasitized crab. Oocytes in the ovary of the host were arrested at pre-vitellogenic stage (pre-vitellogenic oocyte, black arrows). (Right) A crab parasitized by the parasitic barnacle (Sacculina plana) with the female reproductive apparatus (the externa, red arrow) of the parasite on the ventral side of the host’s abdomen (Ab). 


Interestingly, molting of the parasitized hosts are tightly controlled, via regulating the endocrine output (ecdysteroids) of the Y-organ (crustacean molting gland), in manners that facilitate emergency and protection of female reproductive apparatus (the externa) of the parasite.



Control of host’s molting status by the parasite. (Upper) While the host is kept at an an-ecdysial status while harboring externae (yellow tissue in the far left), it re-enters the molt cycle, after larvae are exhaustively spawned from externa and the spent externa falls off from the host, ultimately leading to ecdysis of the host, which is followed immediately by the emergence of a new externa (pink tissue in the far right. (Lower) The intricate control of host’s molting status is achieved by manipulation of endocrine output of the Y-organ by the parasite. A Y-organ tissue section showing a lobe enclosed by a layer of lobular epithelial cells (blue arrows) within which the Y-organ cells (black arrows) are tightly packed and several other lobes completely occulated with infiltrating rootlets of the parasite. Epithelial cell and lumen of the rootlets are pointed by red arrows and labeled L, respectively. 


Regarding sex differentiation, male hosts are feminized by the parasite through modulating endocrine output of the androgenic gland, effectively turning the parasitized host into an anatomical and functional female with a female-shaped abdomen for harboring the externa and production of yolk protein precursors for ovarian maturation in the externa. 



Parasitic feminization. A male crab parasitized by the parasite exhibiting a female-type abdomen (upper), similar to that of a female (lower). 









Parasitic feminization and feminizing factors. Female sacculind larvae infect host of both sexes. When the parasite is sexually mature, its reproductive apparatus, housing the ovary and embryo-incubating chamber (A, black arrow: developing oocyte with yolk granules; blue arrow: developing embryo), protrudes from the abdomen of the host (the externa, see photo posted above). Oocytes maturing inside the externa require vitellogenin (Vg), a female-specific yolk protein precursor that is synthesized in the hepatopancreas of female crustaceans and taken up by maturing ovary during vitellogenesis. According to our recent study, supply of Vg to the externa is contributed at least in part by the host, regardless of its sex (Lee et al., 2021). Male animals, when parasitized, are induced to express Vg (B). In these parasitized males, the androgenic gland (AG), an endocrine gland that is responsible for male sex differentiation through the actions of its secretory hormone the insulin-like androgenic gland hormone (IAG), is infiltrated by the rootlets of the parasite (C, blue arrow: rootlets; red arrow: androgenic cell with large nucleus; yellow arrow: hemocyte), which produce feminizing factor(s) that block expression of IAG (D, NP: non-parasitized; Hit, Hexc, Hexo: various status of parasitization. * indicates significantly different from NP), hence leading to manifestation of various aspects of parasitic feminization including Vg expression (B) and widened abdomen (see photo posted above). We are characterizing the feminizing factor(s) for application in sex manipulation of commercial aquaculture species.




Expression of various immune effectors in the hemocyte and hematopoiesis (production of blood cells) in the hematopoietic tissues of the host are greatly affected by the parasite. Mitotic activity of hematopoietic stem cell is significantly affected by the parasite.



Mitotic activity in the hematopoietic tissue is significantly affected by the parasitic barnacle. Number of mitotic hematopoietic stem cells (brown BrdU labeling) is significantly higher in the non-parasitized (Upper right) than in the parasitized (Upper left) host. Number of circulating hemocyte, specifically hyaline cell, is significantly lower in the parasitized (left) host (Bottom). 


Reference cited 

Chang C-C, Tsai T-W, Hsiao N-W, Chang C-Y, Lin C-L, Watson RD, Lee C-Y. (2010) Structural and functional comparisons and production of recombinant crustacean hyperglycemic hormone (CHH) and CHH-like peptides from the mud crab Scylla olivacea. Gen. Comp. Endocrinol. 167: 68–76.

Chen H-Y, Toullec J-Y and Lee C-Y (2020) The Crustacean Hyperglycemic Hormone Superfamily: Progress Made in the Past Decade. Front. Endocrinol. 11:578958. doi: 10.3389/fendo.2020.578958.

Chen Y.-R., Hsiao N.-W., Huang S.-S., Chang C.-C., Lee Y.-Z., Tsai J.-R., Lin H.-C., Toullec J.-Y., Lee C.-Y., Lyu P.-C. (2020) Structure-based functional study of a peptide of an ecdysozoan superfamily: reveling a common molecular architecture and receptor-interacting residues. bioRxiv doi: https://doi.org/10.1101/2020.10.29.360867

Hsiao C.-J., Wu Y.-I., Wang G.-Y., Tung T.-A., Toullec J-.Y., Liu S.-T., Huang W.-S., Lee C.-Y. (2016) Effects of parasitization by the barnacle Polyascus plana (Cirripedia: Rhizocephala) on a grapsid host Metopograpsus thukuhar: changes in metabolic profile and hemocyte counts. Dis. Aquat. Organ. 119:199-206.

Lai AG, Aboobaker, AA (2017) Comparative genomic analysis of innate immunity reveals novel and conserved components in crustacean food crop species. BMC Genomics 18, 389. https://doi.org/10.1186/s12864-017-3769-4.  

Li W, Chiu KH, Tien YC, Tsai SF, Shih LJ, Lee CH, et al. (2017) Differential effects of silencing crustacean hyperglycemic hormone gene expression on the metabolic profiles of the muscle and hepatopancreas in the crayfish Procambarus clarkii. PloS One 12:e0172557.

Li W, Chiu KH, Lee CY. (2019) Regulation of amino acid and nucleotide metabolism by crustacean hyperglycemic hormone in the muscle and hepatopancreas of the crayfish Procambarus clarkii. PloS One 14:e0221745.

Lin LJ, Chen YJ, Chang YS, Lee CY. Neuroendocrine responses of a crustacean host to viral infection: effects of infection of white spot syndrome virus on the expression and release of crustacean hyperglycemic hormone in the crayfish Procambarus clarkii. Comp Biochem Physiol A Mol Integr Physiol (2013) 164:327–32. 

Liu C.-J., Huang S.-S., Toullec J.-Y., Chang C.-Y., Chen Y.-R., Huang W.-S., Lee C.-Y. (2015) Functional assessment of residues in the amino- and carboxyl-termini of crustacean hyperglycemic hormone (CHH) in the mud crab Scylla olivacea using point-mutated peptides. PloS One 10(8): e0134983.

Miroliubov A, Borisenko I, Nesterenko M, Lianguzova A, Ilyutkin S, Lapshin N, Dobrovolskij A. (2020) Specialized structures on the border between rhizocephalan parasites and their host's nervous system reveal potential sites for host-parasite interactions. Sci. Rep. 10:1128.

Polinski JM, Zimin AV, Clark KF, Kohn AB, Sadowski N, Timp W, Ptitsyn A, Khanna P, Romanova DY, Williams P, Greenwood SJ, Moroz LL, Walt DR, Bodnar AG. The American lobster genome reveals insights on longevity, neural, and immune adaptations. Sci Adv. 2021 Jun 23;7(26):eabe8290. doi: 10.1126/sciadv.abe8290. PMID: 34162536.

Tsai K.-W, Chang S.-G., Wu H.-J, Shih H.-Y., Chen C.-H., Lee C.-Y. (2008) Molecular cloning and differential expression pattern of two structural variants of the crustacean hyperglycemic hormone family from the mud crab Scylla olivacea. Gen. Comp. Endocrinol. 159: 16-25.

World Bank Report No. 83177-GLB (2013) FISH TO 2030: Prospects for Fisheries and Aquaculture. The World Bank, Washington DC 20433, USA


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