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First person – Monika J. Tomecka

机译:第一人称视角– Monika J. Tomecka

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First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Monika Tomecka is first author on ‘ Clinical pathologies of bone fracture modelled in zebrafish ’, published in DMM. Monika conducted the research described in this article while a PhD student in Tom Carney's lab at the Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore and Henry Roehl's lab, Department of Biomedical Science, The University of Sheffield, UK. She is now a CEO at uFraction8, an engineering company that develops biotech instruments for industrial cell culture harvesting. Monika Tomecka How would you explain the main findings of your paper to non-scientific family and friends? Bone fracture injuries, as well as their consequences, are important clinical issues. Several questions raised about them cannot be answered from observations of patients; therefore, animal models of human bone fractures are needed. I have developed zebrafish crush injury as an accurate model for human bone fracture repair. I established the model and further evaluated its usage in the zebrafish bone mutant frf , a known model for osteogenesis imperfecta (OI; also known as brittle bone disease). People with this disease have extremely fragile bones and tend to break them very easily. I tested common human bone disease drugs – bisphosphonates – on the zebrafish crush model, further showing the usefulness and relevance of the model. Upon treatment, I observed a significant impact on fracture healing, as well as on spontaneous fracture formation in juvenile OI zebrafish. Last, but not least, I decided to examine the impact of infection on fracture healing. I introduced controlled infections to the crush site and found that persistent infection inhibits fracture repair. All these results mimic human clinical data. In conclusion, I established a zebrafish bone crush model relevant to human physiology and pathology. I proved its usefulness in bone fracture healing characterisation studies, in determining bone pathogenicity as well as in bone-related drug treatment efficiency, and infection disturbance in bone repair. “The ability to recreate precise genetic lesions offers the ability to provide personalised models for genetic bone disorders of human patients in the near future.” What are the potential implications of these results for your field of research? Whilst studies of amputation of the adult zebrafish tail attracted much interest as a model for regeneration, there has been very limited analysis of the process of repair of bone fractures. Zebrafish crush injury, shown in my paper, is an accurate model for human bone fracture repair and is an enabling tool for human fracture research in fish. To date, the majority of fracture studies were performed in bigger animals such as rodents and dogs. Zebrafish offer a number of advantages as a model system, including ease of imaging and genome modifications, allowing fast generation of bone-specific transgenic lines and mutants. The ability to recreate precise genetic lesions offers the ability to provide personalised models for genetic bone disorders of human patients in the near future. Use of the crush procedure developed here adds to the methods for characterising the ensuing bone phenotype, allowing direct evaluation of the outcome of the genetic lesion on fracture repair. Furthermore, the fertility of zebrafish provides high sample numbers for experimental replicates, whilst compounds are easy to administer through immersion. “It was amazing to find out that zebrafish tail bones can actually be a great model for human bones research.” What has surprised you the most while conducting your research? It was amazing to find out that zebrafish tail bones can actually be a great model for human bones research. It was surprising and amazing to see that most of the results of crush experiments mimicked human clinical data. I have often dealt with disbelief from my peers that ‘fish bones’ can be a good representation of human bones. I was positively surprised when I found and proved that they indeed can. What changes do you think could improve the professional lives of early-career scientists? I truly believe that early-career scientists should focus not only on their studies but also on their personal development, trying to gain new skills and experiences. I think that changes could involve increasing the amount of such opportunities. I am aware that there are already several programmes, workshops, personal development conferences etc., but sometimes their reach is limited or scientists are not convinced about their usefulness. I think we should induce a change of mindset both in early-career scientists and their PIs. Catching opportunities, looking for interdisciplinary solutions and collaborating with industry ar
机译:《第一人称》是对一系列发表在《疾病模型与机制》(DMM)上的论文的第一作者的一系列采访,有助于早期职业研究人员与他们的论文一起发展自我。 Monika Tomecka是DMM出版的“斑马鱼模型的骨折临床病理学”的第一作者。莫妮卡(Monika)在新加坡A * STAR(科学,技术和研究机构)分子与细胞生物学研究所(IMCB)的汤姆·卡尼(Tom Carney)实验室的博士生以及新加坡生物医学系的亨利·罗尔(Henry Roehl)的实验室中进行了本文所述的研究理学,英国谢菲尔德大学。她现在是uFraction8(一家开发用于工业细胞培养收获的生物技术仪器的工程公司)的首席执行官。 Monika Tomecka,您将如何向非科学的家人和朋友解释论文的主要发现?骨骨折损伤及其后果是重要的临床问题。从患者的观察中无法回答关于它们的几个问题。因此,需要人类骨折的动物模型。我已经开发出斑马鱼挤压伤作为人类骨折修复的精确模型。我建立了模型,并进一步评估了其在斑马鱼骨骼突变体frf中的用途,该突变体是成骨不全症(OI;也称为脆性骨病)的已知模型。患有这种疾病的人的骨头极易碎,容易骨折。我在斑马鱼暗恋模型上测试了人类常见的骨疾病药物-双膦酸盐,进一步证明了该模型的有用性和相关性。经过治疗,我观察到了对OI斑马鱼幼年骨折愈合以及自发性骨折形成的重大影响。最后但并非最不重要的一点是,我决定检查感染对骨折愈合的影响。我向挤压部位引入了受控感染,发现持续感染会抑制骨折修复。所有这些结果都模仿了人类的临床数据。最后,我建立了与人类生理学和病理学有关的斑马鱼骨骼挤压模型。我证明了它在骨折愈合特征研究,确定骨致病性以及与骨相关的药物治疗效率以及骨修复中的感染障碍方面的有用性。 “重建精确的遗传病变的能力提供了在不久的将来为人类患者的遗传性骨疾病提供个性化模型的能力。”这些结果对您的研究领域有何潜在影响?虽然将成年斑马鱼尾巴截肢的研究作为再生模型引起了广泛兴趣,但对骨折修复过程的分析却非常有限。我的论文中显示的斑马鱼挤压损伤是人类骨折修复的准确模型,并且是鱼类中人类骨折研究的有效工具。迄今为止,大多数骨折研究都是在较大的动物中进行的,例如啮齿动物和狗。斑马鱼作为模型系统具有许多优势,包括易于成像和基因组修改,可快速生成骨特异性转基因品系和突变体。重建精确的遗传病变的能力提供了在不久的将来为人类患者的遗传性骨疾病提供个性化模型的能力。这里开发的挤压程序的使用增加了表征随后的骨表型的方法,从而可以直接评估遗传损伤在骨折修复上的结果。此外,斑马鱼的繁殖力为实验重复提供了大量的样本,而化合物很容易通过浸泡来施用。 “发现斑马鱼的尾骨实际上可以成为人体骨骼研究的绝佳模型,真是令人惊讶。”在进行研究时,给您最大的惊喜是什么?惊奇地发现,斑马鱼的尾骨实际上可以成为人体骨骼研究的理想模型。看到粉碎实验的大多数结果都模仿了人类临床数据,这真是令人惊讶和惊奇。我经常对同辈的怀疑是“鱼骨头”可以很好地代表人的骨头。当我发现并证明它们确实可以做到时,我感到非常惊讶。您认为哪些变化可以改善早期科学家的职业生活?我坚信,从事早期职业的科学家不仅应专注于研究,而且应着眼于个人发展,以获取新的技能和经验。我认为变革可能涉及增加此类机会的数量。我知道已经有几个程序,讲习班,个人发展会议等,但是有时它们的范围很有限,或者科学家不相信它们的用处。我认为我们应该在早期职业科学家及其效绩指标中引起思维方式的转变。抓住机遇,寻找跨学科的解决方案并与行业机构合作

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