Final Report Summary - TRUST (Training Urology Scientists to develop Treatments)
Urinary Incontinence (UI) affects around 10% of the population (more than 70 Million people in the EU) and unfortunately - due to the aging population - is an increasing cause of impaired quality of life. The most common cause of UI is overactive bladder syndrome (OABS) of which the underlying complex bio-molecular mechanisms are poorly understood. Many distinct tissues (nervous system, urothelium, interstitial cells, smooth muscle cells) contribute to OABS but their specific roles remain unknown. As a result, no effective non-invasive therapy without side effects is available or can be developed without a profound integration of multiple scientific disciplines.
The TRUST ITN is an interdisciplinary research training network of 8 European university institutes and 3 enterprises, with a wide variety of complementary expertise in UI and OABS. The network covers all required disciplines from anatomy, urology, neuroscience, pathology, pharmacology, biomedical engineering, clinical science, bio-informatics to diagnostic- and drug development, that must be applied on cellular-, organ and whole body levels. Currently most researchers are not trained to deal with such a great variety of disciplines, and are thus insufficiently prepared to cope with the modern and increasingly urgent challenges of urology research.
In the TRUST project 11 early stage researchers and 3 experienced researchers received training from different leading European research institutes on multiple complementary disciplines that empowered them to explore and unravel the mechanisms underlying OABS and to develop novel diagnostic, preventative and treatment strategies. Moreover, the integrated research training programme transferred practical skills, knowledge and experience to stimulate successful medical (commercial) exploitation of these results. Finally, the unique multidisciplinary scientific profiles of the researchers has opened up promising career perspectives for the researchers.
A key TRUST achievement was the development of a coherent framework (“TRUST Whole Body LUT Integration Framework”; LUTIF) to draw together complex information from disparate experimental and clinical sources for understandable schematic description. LUTIF provides a contextual basis for scientists and clinicians to place each emerging discovery into its relevant location. This crucially highlights relevance, upstream influences and downstream consequences
Please see Figure 1 in the attachment to this report. It is a schematic of the TRUST Whole Body LUT Integration Framework (LUTIF) showing the key centres of regulatory control at all levels of the neuraxis, their interactions and experimental manipulation. A. The substrates of LUT control, comprising afferent components (sensory and sensation), the efferent components (motor and volition), and the integration centres. Red arrows are used to illustrate the sites of regulation of the default mode of insensate storage (solid), the alternate modes of sensate storage or voiding (double lines) and neonatal voiding (dotted line). B. A mode map illustrating the default mode of insensate storage, used to convey the active components (contrasting with the activity in the alternate modes of sensate storage, voiding, LUT pathophysiology and male genitourinary ejaculation). C. A target map of some of the many studies into structure or function of LUT controls or components investigated by the TRUST partners, showing how the entire system was explored in the experimental programme. MSA: multiple system atrophy; PAG: periaqueductal gray; DAPR: decerebrate artificially perfused rodent; TRP: transient receptor potentials (TRPA1, TRPC1/4, TRPV4); ACh: acetyl choline; TNS: tibial nerve stimulation; PGE2: prostaglandin E2.
LUTIF is a valuable asset for researchers used to working in a focused component of an animal model to appreciate how their work incrementally enhances understanding of lower urinary tract systems physiology, and clinical pathophysiology or therapy. The review drawing together the application of this model using all the experimental results of TRUST, for which the manuscript is in preparation, is a key deliverable achievement of the Whole Body WP. Thus, while three main centres are listed as contributing to the WP, data and published outputs of all sites in the coherent TRUST framework is aligned in the LUTIF exercise, delivering the most detailed systems physiological output in the scientific field for LUT function to date.
The TRUST ITN is an interdisciplinary research training network of 8 European university institutes and 3 enterprises, with a wide variety of complementary expertise in UI and OABS. The network covers all required disciplines from anatomy, urology, neuroscience, pathology, pharmacology, biomedical engineering, clinical science, bio-informatics to diagnostic- and drug development, that must be applied on cellular-, organ and whole body levels. Currently most researchers are not trained to deal with such a great variety of disciplines, and are thus insufficiently prepared to cope with the modern and increasingly urgent challenges of urology research.
In the TRUST project 11 early stage researchers and 3 experienced researchers received training from different leading European research institutes on multiple complementary disciplines that empowered them to explore and unravel the mechanisms underlying OABS and to develop novel diagnostic, preventative and treatment strategies. Moreover, the integrated research training programme transferred practical skills, knowledge and experience to stimulate successful medical (commercial) exploitation of these results. Finally, the unique multidisciplinary scientific profiles of the researchers has opened up promising career perspectives for the researchers.
A key TRUST achievement was the development of a coherent framework (“TRUST Whole Body LUT Integration Framework”; LUTIF) to draw together complex information from disparate experimental and clinical sources for understandable schematic description. LUTIF provides a contextual basis for scientists and clinicians to place each emerging discovery into its relevant location. This crucially highlights relevance, upstream influences and downstream consequences
Please see Figure 1 in the attachment to this report. It is a schematic of the TRUST Whole Body LUT Integration Framework (LUTIF) showing the key centres of regulatory control at all levels of the neuraxis, their interactions and experimental manipulation. A. The substrates of LUT control, comprising afferent components (sensory and sensation), the efferent components (motor and volition), and the integration centres. Red arrows are used to illustrate the sites of regulation of the default mode of insensate storage (solid), the alternate modes of sensate storage or voiding (double lines) and neonatal voiding (dotted line). B. A mode map illustrating the default mode of insensate storage, used to convey the active components (contrasting with the activity in the alternate modes of sensate storage, voiding, LUT pathophysiology and male genitourinary ejaculation). C. A target map of some of the many studies into structure or function of LUT controls or components investigated by the TRUST partners, showing how the entire system was explored in the experimental programme. MSA: multiple system atrophy; PAG: periaqueductal gray; DAPR: decerebrate artificially perfused rodent; TRP: transient receptor potentials (TRPA1, TRPC1/4, TRPV4); ACh: acetyl choline; TNS: tibial nerve stimulation; PGE2: prostaglandin E2.
LUTIF is a valuable asset for researchers used to working in a focused component of an animal model to appreciate how their work incrementally enhances understanding of lower urinary tract systems physiology, and clinical pathophysiology or therapy. The review drawing together the application of this model using all the experimental results of TRUST, for which the manuscript is in preparation, is a key deliverable achievement of the Whole Body WP. Thus, while three main centres are listed as contributing to the WP, data and published outputs of all sites in the coherent TRUST framework is aligned in the LUTIF exercise, delivering the most detailed systems physiological output in the scientific field for LUT function to date.