Jerran Santos is a Postdoctoral Fellow and group leader of the Advanced Tissue Engineering and Drug Delivery Group at the University of Technology Sydney and holds a Honorary Professorship at the University of Toulouse. Dr Santos has established a lab with a strong background in adult stem cells, biomaterials and phenotypic analysis. Dr Santos also established UTS induced pluripotent stem cell lab as well as 3D printing facilities for next generation tissue engineering.
His research focus is in regenerative medicine; utilizing stem cells and biomaterials in developing translational clinical applications. His primary interests are in a systems biology focus of proteomics examining the large shift in a stem cell's proteome during the differentiation into the targeted cell types. The interactions and changes of these proteins over time play an important role in the overall functionality and endpoint cell type. Understanding the underlying molecular mechanisms, pathways and their interactions has a significant role in downstream applications. His interests extend to utilizing stem cells in developing models for degenerative diseases to expand the knowledge database by identifying key pathways in developing diseases.
Current research projects run involve Multiple Sclerosis, Allan-Herndon-Dudley Syndrome, Schizophrenia, Alzheimer's, Osteoarthritis, neural, osteochondral, myogenic differentiation, adult mesenchymal stem cells, induced pluripotent stem cells and and biomaterial synthesis for 3D printing technology for materials and cellular components
Dr Santos has a broad spectrum of expertise in a variety of other areas, which include next generation sequencing of bacterial genomes, venomics, bacterial pathogenesis imbued by secreted moonlighting proteins, cytokine and immuno-modulation by pathogenic bacteria, 3D molecular modelling and interaction network building.
Within UTS, Jerran is a member of the School of Life Sciences Honours Committee as well as the Early Career Researchers Group. Internationally, holds a Honorary Professorship at the University of Toulouse, France.
Professional memberships include Australian Proteomics Society (APS), Tissue Engineering and Regenerative Medicine International Society(TERMIS), International Society for Stem Cell Research (ISSCR) and International Organization of Mycoplasmology (IOM).
Can supervise: YES
He has active research interests in:
· Regenerative Medicine
· Neuronal diseases and traumatic brain and spinal injuries
· Stem Cell biology
· 3D printing
· Biomaterial synthesis and complementation with stem cells
· Medically adaptable materials for tissue engineering
· CRISPR-Cas9 genome editing
· Systems Biology and Interaction Networks
· Functional Proteomics
· Structural Protein Modelling
· Medical implant and drug delivery systems design and synthesis
· Human Degenerative diseases
· Developing disease-in-a-dish models
· Cytokine and immune-regulation
· Bacterial Genomic Sequencing
· Bacterial Moonlighting proteins and pathogenesis
He has over a decade of teaching experience at University of Technology Sydney and Macquarie University. Teaching in a broad spectrum of classes as a lecturer, tutor and lab demonstrator, he believes in engaging with the students in various learning environments to cultivate the best students for postgraduate studies or higher level graduate positions.
• Analytical Biochemistry, 91326
• Cell Biology and Genetics, 91161
• Epidemiology and Public Health Microbiology, 91330
• Fundamentals of Pathophysiology 3, 99636
• Human Anatomy and Physiology, 91400
• Introduction to Pharmacology and Microbiology, 91604
• Molecular Biology 1, 91132
• Molecular Biology 2, 91335
• Proteomics, 91536
• Tissue Engineering, 91560
Dalla, PV, Santos, J, Milthorpe, BK & Padula, MP 2020, 'Selectively-packaged proteins in breast cancer extracellular vesicles involved in metastasis', International Journal of Molecular Sciences, vol. 21, no. 14, pp. 1-16.View/Download from: Publisher's site
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Cancer-derived extracellular vesicles are known to play a role in the progression of the disease. In this rapidly-growing field, there are many reports of phenotypic changes in cells following exposure to cancer-derived extracellular vesicles. This study examines the protein contents of vesicles derived from three well-known breast cancer cell lines, MCF-7, MDA-MB-231 and T47D, using peptide-centric LC-MS/MS and cytokine multiplex immunoassay analysis to understand the molecular basis of these changes. Through these techniques a large number of proteins within these vesicles were identified. A large proportion of these proteins are known to be important in cancer formation and progression and associated with cancer signaling, angiogenesis, metastasis and invasion and immune regulation. This highlights the importance of extracellular vesicles (EVs) in cancer communications and shows some of the mechanisms the vesicles use to assist in cancer progression.
Fajardo, J, Milthorpe, BK & Santos, J 2020, 'Molecular Mechanisms Involved in Neural Substructure Development during Phosphodiesterase Inhibitor Treatment of Mesenchymal Stem Cells.', International journal of molecular sciences, vol. 21, no. 14.View/Download from: Publisher's site
Stem cells are highly important in biology due to their unique innate ability to self-renew and differentiate into other specialised cells. In a neurological context, treating major injuries such as traumatic brain injury, spinal cord injury and stroke is a strong basis for research in this area. Mesenchymal stem cells (MSC) are a strong candidate because of their accessibility, compatibility if autologous, high yield and multipotency with a potential to generate neural cells. With the use of small-molecule chemicals, the neural induction of stem cells may occur within minutes or hours. Isobutylmethyl xanthine (IBMX) has been widely used in cocktails to induce neural differentiation. However, the key molecular mechanisms it instigates in the process are largely unknown. In this study we showed that IBMX-treated mesenchymal stem cells induced differentiation within 24 h with the unique expression of several key proteins such as Adapter protein crk, hypoxanthine-guanine phosphoribosyltransferase, DNA topoisomerase 2-beta and Cell division protein kinase 5 (CDK5), vital in linking signalling pathways. Furthermore, the increased expression of basic fibroblast growth factor in treated cells promotes phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) cascades and GTPase-Hras interactions. Bioinformatic and pathway analyses revealed upregulation in expression and an increase in the number of proteins with biological ontologies related to neural development and substructure formation. These findings enhance the understanding of the utility of IBMX in MSC neural differentiation and its involvement in neurite substructure development.
Santos, J, Hubert, T & Milthorpe, BK 2020, 'Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways.', Cells, vol. 9, no. 3.View/Download from: Publisher's site
Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells.
Pelegri, NG, Gorrie, CA & Santos, J 2019, 'Rat Hippocampal Neural Stem Cell Modulation Using PDGF, VEGF, PDGF/VEGF, and BDNF.', Stem cells international, vol. 2019.View/Download from: Publisher's site
Neural stem cells have become the focus of many studies as they have the potential to differentiate into all three neural lineages. This may be utilised to develop new and novel ways to treat neurological conditions such as spinal cord and brain injuries, especially if the stem cells can be modulated in vivo without additional invasive surgical procedures. This research is aimed at investigating the effects of the growth factors vascular endothelial growth factor, platelet-derived growth factor, brain-derived neurotrophic factor, and vascular endothelial growth factor/platelet-derived growth factor on hippocampal-derived neural stem cells. Cell growth and differentiation were assessed using immunohistochemistry and glutaminase enzyme assay. Cells were cultured for 14 days and treated with different growth factors at two different concentrations 20 ng/mL and 100 ng/mL. At 2 weeks, cells were fixed, and immunohistochemistry was conducted to determine cellular differentiation using antibodies against GFAP, nestin, OSP, and NF200. The cell medium supernatant was also collected during treatment to determine glutaminase levels secreted by the cells as an indicator of neural differentiation. VEGF/PDGF at 100 ng/mL had the greatest influence on cellular proliferation of HNSC, which also stained positively for nestin, OSP, and NF200. In comparison, HNSC in other treatments had poorer cell health and adhesion. HNSC in all treatment groups displayed some differentiation markers and morphology, but this is most significant in the 100 ng/ml VEGF/PDGF treatment. VEGF/PDGF combination produced the optimal effect on the HNSCs inducing the differentiation pathway exhibiting oligodendrocytic and neuronal markers. This is a promising finding that should be further investigated in the brain and spinal cord injury.
Santos, J, Milthorpe, BK & Padula, MP 2019, 'Correction: Santos, J., et al. Proteomic Analysis of Cyclic Ketamine Compounds Ability to Induce Neural Differentiation in Human Adult Mesenchymal Stem Cells. International Journal of Molecular Sciences 2019, 20, 523.', International journal of molecular sciences, vol. 20, no. 14.View/Download from: Publisher's site
The authors wish to make the following corrections to this paper [...].
Santos, J, Milthorpe, BK & Padula, MP 2019, 'Proteomic Analysis of Cyclic Ketamine Compounds Ability to Induce Neural Differentiation in Human Adult Mesenchymal Stem Cells.', International journal of molecular sciences, vol. 20, no. 3.View/Download from: Publisher's site
Neural regeneration is of great interest due to its potential to treat traumatic brain injuries and diseases that impact quality of life. Growth factor mediated differentiation can take up to several weeks to months to produce the cell of interest whereas chemical stimulation may be as minimal as a few hours. The smaller time scale is of great clinical relevance. Adipose derived stem cells (ADSCs) were treated for up to 24 h with a novel differentiation media containing the cyclic ketamine compounds to direct neurogenic induction. The extent of differentiation was investigated by proteome changes occurring during the process. The treatments indicated the ADSCs responded favorably to the neurogenic induction media by presenting a number of morphological cues of neuronal phenotype previously seen and a higher cell population post induction compared to previous studies. Furthermore, approximately 3500 proteins were analyzed and identified by mass spectrometric iTRAQ analyses. The bioinformatics analyses revealed hundreds of proteins whose expression level changes were statistically significant and biologically relevant to neurogenesis and annotated as being involved in neurogenic development. Complementing this, the Bioplex cytokine assay profiles present evidence of decreased panel of stress response cytokines and a relative increase in those involved in neurogenesis.
Tonga, KO, King, GG, Farah, CS, Thamrin, C, Tang, FS, Santos, J, Sharma, P, Chapman, DG & Oliver, BG 2018, 'Steroid insensitive fixed airflow obstruction is not related to airway inflammation in older non-smokers with asthma.', Respiratory research, vol. 19, no. 1, pp. 176-176.View/Download from: Publisher's site
There is limited evidence linking airway inflammation and lung function impairment in older non-smoking asthmatics with fixed airflow obstruction (FAO), which can develop despite treatment with inhaled corticosteroids (ICS). We assessed lung function (spirometry, forced oscillation technique (FOT)), lung elastic recoil and airway inflammation using bronchoalveolar lavage (BAL) in non-smoking adult asthmatics with FAO, following 2 months treatment with high-dose ICS/long-acting beta-agonist. Subjects demonstrated moderate FAO, abnormal FOT indices and loss of lung elastic recoil. This cross-sectional study showed a lack of a relationship between BAL neutrophils, eosinophils, inflammatory cytokines and lung function impairment. Other inflammatory pathways or the effect of inflammation on lung function over time may explain FAO development.
Wong, SL, To, J, Santos, J, Allam, VSRR, Dalton, JP, Djordjevic, SP, Donnelly, S, Padula, MP & Sukkar, MB 2018, 'Proteomic Analysis of Extracellular HMGB1 Identifies Binding Partners and Exposes Its Potential Role in Airway Epithelial Cell Homeostasis.', Journal of Proteome Research, vol. 17, no. 1, pp. 33-45.View/Download from: Publisher's site
The release of damage-associated molecular patterns (DAMPs) by airway epithelial cells is believed to play a crucial role in the initiation and development of chronic airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Intriguingly, the classic DAMP high-mobility group box-1 (HMGB1) is detected in the culture supernatant of airway epithelial cells under basal conditions, indicating a role for HMGB1 in the regulation of epithelial cellular and immune homeostasis. To gain contextual insight into the potential role of HMGB1 in airway epithelial cell homeostasis, we used the orthogonal and complementary methods of high-resolution clear native electrophoresis, immunoprecipitation, and pull-downs coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile HMGB1 and its binding partners in the culture supernatant of unstimulated airway epithelial cells. We found that HMGB1 presents exclusively as a protein complex under basal conditions. Moreover, protein network analysis performed on 185 binding proteins revealed 14 that directly associate with HMGB1: amyloid precursor protein, F-actin-capping protein subunit alpha-1 (CAPZA1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH), ubiquitin, several members of the heat shock protein family (HSPA8, HSP90B1, HSP90AA1), XRCC5 and XRCC6, high mobility group A1 (HMGA1), histone 3 (H3F3B), the FACT (facilitates chromatin transcription) complex constituents SUPT1H and SSRP1, and heterogeneous ribonucleoprotein K (HNRNPK). These studies provide a new understanding of the extracellular functions of HMGB1 in cellular and immune homeostasis at the airway mucosal surface and could have implications for therapeutic targeting.
Macha, IJ, Ben-Nissan, B, Santos, J, Cazalbou, S, Stamboulis, A, Grossin, D & Giordano, G 2017, 'Biocompatibility of a new biodegradable polymer-hydroxyapatite composite for biomedical applications', Journal of Drug Delivery Science and Technology, vol. 38, pp. 72-77.View/Download from: Publisher's site
© 2017 Elsevier B.V. The rise in the number of musculoskeletal disorders (MSDs) due to an increasingly aging population has led to a growing demand for medication to prevent and treat these diseases. An increased interest in the development of new drugs to allow treatment of these diseases in their very early stages is currently observed. The current approach on local direct delivery of medication and key minerals to support bone repair and regeneration at the defect site, from flexible degradable devices, seems to be an effective strategy. Polylactic acid (PLA) and microspheres of hydrothermally converted coralline hydroxyapatite (cHAp) were used to develop PLA thin film composites as drug delivery systems. The PLA provided flexibility and biodegradability of the systems, while coralline hydroxyapatite provided the required calcium and phosphate ions for bone regeneration. These coralline hydroxyapatite microspheres have a unique architecture of interconnected porosity, are bioactive in nature and suitable for drug loading and controlled slow drug release. The cell attachment and morphology of the PLA thin film composites were evaluated in vitro using cell cultures of human adipose derived stem cells (hADSC). It was shown that hADSC cells exhibited a strong attachment and proliferation on PLA thin film-cHAp composites, signifying high biocompatibility and a potential for osteointegration due to the presence of HAp.
Padula, MP, Berry, IJ, O Rourke, MB, Raymond, BBA, Santos, J & Djordjevic, SP 2017, 'A Comprehensive Guide for Performing Sample Preparation and Top-Down Protein Analysis.', Proteomes, vol. 5, no. 2.View/Download from: Publisher's site
Methodologies for the global analysis of proteins in a sample, or proteome analysis, have been available since 1975 when Patrick O'Farrell published the first paper describing two-dimensional gel electrophoresis (2D-PAGE). This technique allowed the resolution of single protein isoforms, or proteoforms, into single 'spots' in a polyacrylamide gel, allowing the quantitation of changes in a proteoform's abundance to ascertain changes in an organism's phenotype when conditions change. In pursuit of the comprehensive profiling of the proteome, significant advances in technology have made the identification and quantitation of intact proteoforms from complex mixtures of proteins more routine, allowing analysis of the proteome from the 'Top-Down'. However, the number of proteoforms detected by Top-Down methodologies such as 2D-PAGE or mass spectrometry has not significantly increased since O'Farrell's paper when compared to Bottom-Up, peptide-centric techniques. This article explores and explains the numerous methodologies and technologies available to analyse the proteome from the Top-Down with a strong emphasis on the necessity to analyse intact proteoforms as a better indicator of changes in biology and phenotype. We arrive at the conclusion that the complete and comprehensive profiling of an organism's proteome is still, at present, beyond our reach but the continuing evolution of protein fractionation techniques and mass spectrometry brings comprehensive Top-Down proteome profiling closer.
Santos, J, Milthorpe, BK, Herbert, BR & Padula, MP 2017, 'Proteomic Analysis of Human Adipose Derived Stem Cells during Small Molecule Chemical Stimulated Pre-neuronal Differentiation.', International journal of stem cells, vol. 10, no. 2, pp. 193-217.View/Download from: Publisher's site
Adipose derived stem cells (ADSCs) are acquired from abdominal liposuction yielding a thousand fold more stem cells per millilitre than those from bone marrow. A large research void exists as to whether ADSCs are capable of transdermal differentiation toward neuronal phenotypes. Previous studies have investigated the use of chemical cocktails with varying inconclusive results.Human ADSCs were treated with a chemical stimulant, beta-mercaptoethanol, to direct them toward a neuronal-like lineage within 24 hours. Quantitative proteomics using iTRAQ was then performed to ascertain protein abundance differences between ADSCs, beta-mercaptoethanol treated ADSCs and a glioblastoma cell line.The soluble proteome of ADSCs differentiated for 12 hours and 24 hours was significantly different from basal ADSCs and control cells, expressing a number of remodeling, neuroprotective and neuroproliferative proteins. However toward the later time point presented stress and shock related proteins were observed to be up regulated with a large down regulation of structural proteins. Cytokine profiles support a large cellular remodeling shift as well indicating cellular distress.The earlier time point indicates an initiation of differentiation. At the latter time point there is a vast loss of cell population during treatment. At 24 hours drastically decreased cytokine profiles and overexpression of stress proteins reveal that exposure to beta-mercaptoethanol beyond 24 hours may not be suitable for clinical application as our results indicate that the cells are in trauma whilst producing neuronal-like morphologies. The shorter treatment time is promising, indicating a reducing agent has fast acting potential to initiate neuronal differentiation of ADSCs.
Charoensuk, T, Sirisathitkul, C, Boonyang, U, Macha, IJ, Santos, J, Grossin, D & Ben-Nissan, B 2016, 'In vitro bioactivity and stem cells attachment of three-dimensionally ordered macroporous bioactive glass incorporating iron oxides', JOURNAL OF NON-CRYSTALLINE SOLIDS, vol. 452, pp. 62-73.View/Download from: Publisher's site
Macha, IJ, Ben-Nissan, B, Santos, J, Cazalbou, S & Milthorpe, B 2016, 'Hydroxyapatite/PLA biocomposite thin films for slow drug delivery of antibiotics for the treatment of bone and implant-related infections', Key Engineering Materials, vol. 696, pp. 271-276.View/Download from: Publisher's site
© 2016 Trans Tech Publications, Switzerland. Drug delivery systems were developed from coralline hydroxyapatite (HAp) and biodegradable polylactic acid (PLA). Gentamicin (GM) was loaded in either directly to PLA (PLAGM) or in HAp microspheres. Drug loaded HAp was used to make thin film composites (PLAHApGM). Dissolution studies were carried out in phosphate buffered saline (PBS). The release profiles suggested that HAp particles improved drug stabilization and availability as well controlled the release rate. The release also displays a steady state release. In vitro studies in human Adipose Derived Stem Cells (hADSCs) showed substantial quantities of cells adhering to hydroxyapatite containing composites. The results suggested that the systems could be tailored to release different clinical active substances for a wide range of biomedical applications.
Jarocki, VM, Santos, J, Tacchi, JL, Raymond, BBA, Deutscher, AT, Jenkins, C, Padula, MP & Djordjevic, SP 2015, 'MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae', Open Biology, vol. 5, no. 1, pp. 1-13.View/Download from: Publisher's site
Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides. Mycoplasma hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461 (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of M. hyopneumoniae.
Wyrsch, E, Roy Chowdhury, P, Abraham, S, Santos, J, Darling, AE, Charles, IG, Chapman, TA & Djordjevic, SP 2015, 'Comparative genomic analysis of a multiple antimicrobial resistant enterotoxigenic E. coli O157 lineage from Australian pigs.', BMC Genomics, vol. 16, pp. 1-11.View/Download from: Publisher's site
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) are a major economic threat to pig production globally, with serogroups O8, O9, O45, O101, O138, O139, O141, O149 and O157 implicated as the leading diarrhoeal pathogens affecting pigs below four weeks of age. A multiple antimicrobial resistant ETEC O157 (O157 SvETEC) representative of O157 isolates from a pig farm in New South Wales, Australia that experienced repeated bouts of pre- and post-weaning diarrhoea resulting in multiple fatalities was characterized here. Enterohaemorrhagic E. coli (EHEC) O157:H7 cause both sporadic and widespread outbreaks of foodborne disease, predominantly have a ruminant origin and belong to the ST11 clonal complex. Here, for the first time, we conducted comparative genomic analyses of two epidemiologically-unrelated porcine, disease-causing ETEC O157; E. coli O157 SvETEC and E. coli O157:K88 734/3, and examined their phylogenetic relationship with EHEC O157:H7. RESULTS: O157 SvETEC and O157:K88 734/3 belong to a novel sequence type (ST4245) that comprises part of the ST23 complex and are genetically distinct from EHEC O157. Comparative phylogenetic analysis using PhyloSift shows that E. coli O157 SvETEC and E. coli O157:K88 734/3 group into a single clade and are most similar to the extraintestinal avian pathogenic Escherichia coli (APEC) isolate O78 that clusters within the ST23 complex. Genome content was highly similar between E. coli O157 SvETEC, O157:K88 734/3 and APEC O78, with variability predominantly limited to laterally acquired elements, including prophages, plasmids and antimicrobial resistance gene loci. Putative ETEC virulence factors, including the toxins STb and LT and the K88 (F4) adhesin, were conserved between O157 SvETEC and O157:K88 734/3. The O157 SvETEC isolate also encoded the heat stable enterotoxin STa and a second allele of STb, whilst a prophage within O157:K88 734/3 encoded the serum survival gene bor. Both isolates harbor a large repertoire of antibi...
Chou, J, Valenzuela, SM, Santos, J, Bishop, D, Milthorpe, B, Green, DW, Otsuka, M & Ben-Nissan, B 2014, 'Strontium- and magnesium-enriched biomimetic beta-TCP macrospheres with potential for bone tissue morphogenesis', JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 8, no. 10, pp. 771-778.View/Download from: Publisher's site
Darling, AE, McKinnon, J, Santos, J, Charles, IG, Roy Chowdhury, P, Djordjevic, S & Worden, P 2014, 'A draft genome of Escherichia coli sequence type 127 strain 2009-46.', Gut Pathogens, vol. Sept 1, no. 6, pp. 32-32.View/Download from: Publisher's site
Green, DW, Padula, M, Santos, J, Chou, J, Milthorpe, BK & Ben-Nissan, B 2013, 'A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration.', Marine Drugs, vol. 11, no. 4, pp. 1203-1220.View/Download from: Publisher's site
A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP) and transforming growth factor beta (TGF-ß) exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use.
Marcon, F, Purtell, LA, Santos, J, Hains, PG, Escoubas, P, Graudins, A & Nicholson, GM 2013, 'Characterization of monomeric and multimeric snake neurotoxins and other bioactive proteins from the venom of the lethal Australian common copperhead (Austrelaps superbus)', Biochemical Pharmacology, vol. 85, no. 10, pp. 1555-1573.View/Download from: Publisher's site
Envenomation by Australian copperheads results mainly in muscle paralysis largely attributed to the presence of postsynaptic a-neurotoxins. However, poorly reversible neurotoxic effects suggest that these venoms may contain snake presynaptic phospholipase A2 neurotoxins (SPANs) that irreversibly inhibit neurotransmitter release. Using size-exclusion liquid chromatography, the present study isolated the first multimeric SPAN complex from the venom of the Australian common copperhead, Austrelaps superbus. The multimeric SPAN P-elapitoxin-As1a (P-EPTX-As1a) along with two novel monomeric SPANs and a new postsynaptic a-neurotoxin were then pharmacologically characterized using the chick biventer cervicis nerve-muscle preparation. All SPANs inhibited nerve-evoked twitch contractions at the neuromuscular junction without inhibiting contractile responses to cholinergic agonists or KCl. These actions are consistent with a prejunctional action to inhibit neurotransmitter release, without direct myotoxicity. Furthermore, the multimeric P-EPTX-As1a caused tetanic `fade in muscle tension under high frequency nerve stimulation, and produced a triphasic alteration to neurotransmitter release. These actions have been previously noted with other multimeric SPAN complexes such as taipoxin. Moreover, the neurotoxic a-subunit of P-EPTX-As1a shows high homology to taipoxin a-chain. Several other coagulopathic and myotoxic high mass proteins including a class PIII snake venom metalloproteinase, C- type lectin, L-amino acid oxidase, acetylcholinesterase and phospholipase B were also identified that may contribute to the overall toxicity of A. superbus venom. In conclusion, clinicians should be aware that early antivenom intervention might be necessary to prevent the onset of irreversible presynaptic neurotoxicity caused by multimeric and monomeric SPANs and that A. superbus venom is potentially capable of producing coagulopathic and myotoxic effects.
Green, D, Padula, M, Santos, J, Chou, J, Milthorpe, BK & Ben-Nissan, B 2012, 'A new role for marine skeletal proteins in regenerative orthopaedics', Key Engineering Materials (Volumes 529 - 530) bioceramics 24, Bioceramics, Scientific.net, Fukuoka, Japan, pp. 654-659.View/Download from: Publisher's site
Use of ready-made marine skeletons is one of the simplest possible remedies to major problems hindering the future development of regenerative orthopaedics- such as, providing a richness of framework designs and now a potentially rich, accessible source
External Partners include:
Matraville Medical Complex
Sherman Family Foundation
University of Toulouse
University of Birmingham