IRTG PhD program
The International Research Training Group (IRTG) between Monash and Justus-Liebig Universities
What is the Monash-JLU IRTG?
A research doctoral training program was established in 2013 and has continued for over 10 years between Monash University in Melbourne, Australia and Justus-Liebig University (JLU) in Giessen, Germany. Its hallmark feature is the enrolment of over 30 PhD students into an International Research Training Group (IRTG), funded by the German government and by Monash University, in projects lead jointly by investigators at both institutions.
The overall goal of the program has been to train a new generation of PhD scientists, equipping them with the skills, knowledge and collaborations to tackle critical global health issues in the area of male reproductive health. The Monash-JLU IRTG fostered a strong environment for intellectual growth, creating innovation and knowledge through its strategic investment in leading edge research and in PhD student training.
Collaborative research projects involved chief investigators/supervisors from both Monash and JLU, working together with students who spent time in labs in both countries. The IRTG capitalised on the unique combination of research resources at each institution, including experimental models, platform technologies and exceptional catalogue of well-described human clinical samples.
Monash and JLU scientists, clinicians and students pictured at JLU, Giessen
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A collaborative research program into male reproductive health disorders
The Monash-JLU IRTG “Molecular Pathogenesis of Male Reproductive Disorders” brought together a large team (>30) of international experts in male reproductive medicine, including both basic research scientists and clinicians treating men with a range of reproductive disorders. These experts trained PhD and medical students in male reproductive health, with the PhD students having the opportunity to be awarded a joint-badged PhD from both Monash and JLU.
According to the World Health Organisation, reproductive and sexual health issues account for 14% of the global burden of ill-health in men. The IRTG program offered students a focus on bench-to-bedside approaches to diagnose and treat men’s reproductive health disorders. In 20 research projects, led jointly by investigators at each institution, innovative research strategies were applied with the goal of discovering new therapies for the diagnosis and treatment of male infertility, testicular and prostate cancers, and inflammatory disorders of the male reproductive tract.
Male reproductive tract disorders are common, with infertility and prostate disease being particularly prevalent. Whilst infertility and testicular cancer are of major importance in younger men of ‘reproductive age’, prostate disease, such as benign prostate hyperplasia (BPH), prostate cancer, lower urinary tract symptoms (LUTS), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) occur most frequently in older men. The male reproductive organs are also susceptible to inflammatory diseases mediated by the immune system; these can impact on fertility and/or prostate function, causing disorders such as orchitis (inflammation of the testis), epididymitis (inflammation of the epididymis) and CP/CPPS. All projects in this program investigated clinically relevant aspects of these disorders of male reproductive functions, including pathogenesis, treatment and/or diagnosis.
The joint PhD program
Teams of research scientists, clinicians and postgraduate students worked on 20 projects, each tackling different aspects of male reproductive health issues. These projects were led by experts in testis, epididymal and prostate biology, epigenetics, immunology, cell biology, endocrinology and andrology.
PhD students were trained within two world-leading Reproductive Biology research centres at Monash and JLU. Students received specialised training in a wide variety of research areas, including infertility, immunology and inflammation, reproductive hormones and local factors, and TGFβ/activin superfamily biology. They attended lectures and workshops from world-leading scientists, round table discussions with clinicians and other health experts, had visits to hospitals and technology facilities and enjoyed bespoke training opportunities to capitalise on the local strengths at each institution.
While at JLU, students had access to an excellent training program via the International Giessen Graduate Centre for the Life Sciences (GGL). At Monash, students also received targeted training in research investigation, science communications, statistics, bioinformatics and career development and were mentored by senior research scientists.
Students who enrolled in the program and satisfied certain criteria were awarded a joint PhD from both universities. All who completed the program reported that their projects and personal experience were enhanced by interactions with multiple supervisors, gaining from each individual’s knowledge and technical expertise.
A longstanding collaboration between Monash and JLU
This collaborative program evolved from a long standing cooperation between Monash scientists and Professor Andreas Meinhardt, who completed postdoctoral training at Monash in the mid-1990s. Prof Dr Meinhardt, now Director of the Institute of Anatomy and Cell Biology at JLU, has worked with several Monash researchers over the years and now oversees teams of scientists at JLU working on multiple male reproductive health disorders.
In 2012, Prof Kate Loveland, then an NHMRC Senior Research Fellow at the Hudson Institute and Monash University, and Prof Dr Meinhardt led a plan to draw together specialists in male reproductive health at both Universities. Researchers from both countries came together to identify a series of strategic goals and developed projects that leveraged their special skills and research tools to tackle the diagnosis and treatment of important men’s reproductive health disorders.
The program drew together researchers with common interests and a long history of collaboration from different sites across Monash University. Researchers based at many sites across Monash participated in collaborative research and contributed their individual areas of expertise to the doctoral training program, including scientists from Hudson Institute of Medical Research (School of Clinical Sciences at Monash Health), the Monash Biomedicine Discovery Institute (Faculty of Medicine, Nursing and Health Sciences), the School of Biological Sciences (Faculty of Science), the Australian Medical Research Institute (ARMI) and the Monash Institute of Pharmaceutical Sciences.
The first program, funded by the German Research Foundation (DFG), with further support from Justus-Liebig University (JLU) and Monash University, facilitated 9 collaborative research projects. The program was highly successful, resulting in more than 25 joint publications and training of more than 15 postgraduate students, many of whom received awards for their work from scientific societies and other organisations.
Following the success of the first IRTG program, the global team applied for a renewal to the DFG in 2016, to support 11 further research projects and 22 postgraduate students. The program was rated very highly by the DFG and funding was renewed in May 2017. This renewal funding provided more than € 4.15 million ($6.24 million AUD) for the research partnership to allow its continuation until the end of 2022. JLU provided additional funds to support various aspects of the research, including access for JLU students to the world-class research platforms for biomedical research at Monash, and the collaborative work continues.
Monash University also provided extensive financial support for the IRTG. Monash and the Faculty of Medicine Nursing and Health Sciences committed more than $500,000, along with 11 tuition and living stipend scholarships, that was used to support students enrolled through Monash in the 2017-2022 funding period.
Areas of research in the 2017-2022 IRTG
The program was organised into 11 projects, each managed by a team of both Monash and JLU researchers. Each project included up to 3 PhD students working on different project aspects simultaneously, and several of these are ongoing (as of May 2023) while students remain enrolled and actively engaged in research.
- Sperm morphology and motility in mice and men: Investigations of defective male germ cell differentiation. Supervisors: Germany: D. Fietz and M. Bergmann (JLU); Australia: M. O’Bryan and L. O’Donnell (Monash)
- Human testis cancer and spermatogenesis control by immune cells. Supervisors: Germany: M. Bergmann, H.-Chr. Schuppe and F. Wagenlehner (JLU), Australia: K. Loveland, M. Hedger and R. Hobbs (Monash), B.E. Loveland (collaborator)
- Formation of the testicular immunological barrier through immune modulation by somatic cells. Supervisors: Germany: L. Konrad, G. Scheiner-Bobis (JLU), Australia: K. Loveland and P.G. Stanton (Monash), B. Loveland and M. Baker (collaborators) (project based at Hudson Institute, Clayton)
- Proteomics in seminal plasma and testicular interstitial fluid as predictor of successful sperm retrieval in infertile azoospermic men. Supervisors: Germany: T. Diemer, D. Fietz and A. Pilatz (JLU), Australia: P.G. Stanton, L. O’Donnell and R.I. McLachlan (Monash)
- Systemic and local inflammatory gene regulation and redox-signalling in chronic prostatitis – studies in patients’ blood and ejaculates towards individualized disease profiling. Supervisors: Germany: F. Wagenlehner and U. Schagdarsurengin (JLU), Australia: B Extintaris and G. Risbridger (Monash)
- Hormonal regulation of cGMP pathways and spontaneous contractility in the prostate. Supervisors: Germany: R. Middendorff (JLU), Australia: G. Risbridger and B. Exintaris (Monash) (project based at Monash Institute of Pharmaceutical Sciences, Parkville)
- The role of activins and MCP-1/CCL2 in the development of CD4+CD8+ T cells and fibrotic responses during chronic testicular inflammation in mice. Supervisors: Germany: M. Fijak and S. Bhushan (JLU), Australia: M. Hedger and K. Loveland (Monash) (project based at Hudson Institute, Clayton)
- Targeting the TGFβ superfamily to prevent fibrosis of the epididymis and preserve fertility following bacterial infection. Supervisors: Germany: A. Meinhardt and R. Middendorff (JLU), Australia: M. Hedger and K. Loveland (Monash)
- Regulation of immune responses in the normal and infected testis: role of Sertoli cell-derived activins. Supervisors: Germany: A. Meinhardt and S. Bhushan (JLU), Australia: M. Hedger and K. Loveland (Monash)
- Impacts of epigenetic interactions between TET1 and PRC2 in spermatogenesis and fertility. Supervisors: Germany: U. Schagdarsurengin and K. Steger (JLU), Australia: P. Western (Monash) (project based at Hudson Institute, Clayton)
- Role of oxytocin in the contractility of the male reproductive tract: implications for the treatment of benign prostatic hyperplasia. Supervisors: Germany: R. Middendorff, T. Linn and F. Wagenlehner (JLU), Australia: B. Exintaris and G. Risbridger (Monash), M. Whittaker (collaborator) (project based at Monash Institute of Pharmaceutical Sciences, Parkville)
Key outcomes of the Monash-JLU IRTG
This highly successful program has so far produced 23 PhD graduates, more than 250 student presentations at national and international meetings, and 75 professional awards to PhDs and postdocs.
Monash investigator outcomes were enhanced by the Monash-JLU IRTG engagement. For research project grants awarded during the 2017-2022 funding interval included seven National Health and Medical Research Council (NHMRC) Grants (total A$ 6.8m), three ARC Grants (A$ 1.5m) and one NHMRC Fellowship renewal ($ 145,607).
More than 60 publications authored by Monash and JLU investigators and students were produced from by the IRTG, and further publications will result as collaborations continue in 2023 and beyond.
Examples of recent Monash-JLU joint publications are listed below (IRTG investigators and students names in bold).
Hosseini S, Moody SC, Fietz D, Indumathy S, Schuppe HC, Hedger MP, Loveland KL. The changing landscape of immune cells in the fetal mouse testis. Histochem Cell Biol. 2022;158(4):345-368.
Pleuger C, Ai D, Hoppe ML, Winter LT, Bohnert D, Karl D, Guenther S, Epelman S, Kantores C, Fijak M, Ravens S, Middendorff R, Mayer JU, Loveland KL, Hedger M, Bhushan S, Meinhardt A. (2022): The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis. In Elife; e82193. DOI: 10.7554/eLife.82193. PMID: 36515584.
Wijayarathna R, Genovese R, Meinhardt A, Loveland KL, Groome NP, Hinton BT, Hedger MP. (2022): Examination of testicular lumicrine regulation of activins and immunoregulatory genes in the epididymal caput. In: Andrology (1):190-201. DOI: 10.1111/andr.13099. PMID: 34415685.
Seidensticker M, Tasch S, Mietens A, Exintaris B, Middendorff R. (2022): Treatment of benign prostatic hyperplasia and abnormal ejaculation: live imaging reveals tamsulosin - but not tadalafil - induced dysfunction of prostate, seminal vesicles and epididymis. In: Reproduction; 164(6):291-301. DOI: 10.1530/REP-22-0197. PMID: 36173812
Biniwale S, Wijayarathna R, Pleuger C, Bhushan S, Loveland KL, Meinhardt A, Hedger MP. Regulation of macrophage number and gene transcript levels by activin A and its binding protein, follistatin, in the testes of adult mice. J Reprod Immunol. 2022 Jun;151:103618. doi: 10.1016/j.jri.2022.103618. Epub 2022 Mar 26. PMID: 35378491
O'Donnell L, Rebourcet D, Dagley LF, Sgaier R, Infusini G, O'Shaughnessy PJ, Chalmel F, Fietz D, Weidner W, Legrand JMD, Hobbs RM, McLachlan RI, Webb AI, Pilatz A, Diemer T, Smith LB, Stanton PG. Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men. FASEB J. 2021 Mar; 35(3):e21397. doi: 10.1096/fj.202002484R. PMID: 33565176
Lee SN, Kraska J, Papargiris M, Teng L, Niranjan B, Hammar J, Ryan A, Frydenberg M, Lawrentschuk N, Middendorff R, Ellem SJ, Whittaker M, Risbridger GP, Exintaris B. Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate. Sci Rep. 2021 Mar 18;11(1):6352. doi: 10.1038/s41598-021-85439-4. PMID: 33737570
Stadler B, Nowell CJ, Whittaker MR, Arnhold S, Pilatz A, Wagenlehner FM, Exintaris B, Middendorff R. Physiological and pharmacological impact of oxytocin on epididymal propulsion during the ejaculatory process in rodents and men. FASEB J. 2021 Jun;35(6):e21639. doi: 10.1096/fj.202100435R. PMID: 34041782