Determining the metabolic and molecular mechanisms to enhance magnetosome biomanufacturing
确定增强磁小体生物制造的代谢和分子机制
基本信息
- 批准号:BB/V010603/1
- 负责人:
- 金额:$ 56.14万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2021
- 资助国家:英国
- 起止时间:2021 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Today's economy relies to a large extent on the petrochemical industries that provide us with fuels, chemicals and materials that are used by our society. The petroleum-based sectors are worth around £50bn to the UK economy each year. However, this is not sustainable due to the negative impact of net carbon emissions on the environment. The UK is committed to move to a net zero carbon economy by 2050 and this means that we need to develop alternative processes to replace petroleum. Bio-technologies therefore offer a huge potential to impact on the bioeconomy to mitigate climate change through the development of greener, cleaner manufacturing processes and new products that benefit the society through the use of living organisms.There exist a family of microorganisms called magnetotactic bacteria (MTB) that are well known because they can make tiny crystals of iron called magnetosomes that allow them to function like a compass, and point to the earth's magnetic north pole. Magnetosomes are "nanomagnets" that can be used as an innovative alternative to traditional chemical magnetic nanoparticles (MNPs) because of their advantageous and unique properties. Their applications include for example, cancer treatment, MRI contrast agents and metal capturing. Therefore, magnetosomes have the potential to become the next generation of biological MNPs produced using environmentally friendly routes. However, future widespread applications of magnetosomes will, to a large extend, depend on the challenging development of intensified high-yielding biomanufacturing. We can use the MTB model such as Magnetospirillum gryphiswaldense (Mgryph) to address this challenge. We have previously developed a methodology to produce and characterise magnetosomes and have recently discovered that the nutritional requirements of Mgryph are significantly different when grown in the presence or limitation of air. Importantly, we do not yet understand the biological mechanisms by which magnetosome production in Mgryph can be improved. This information is essential to develop optimised biomanufacturing and realise the full potential of magnetosomes for further application studies and commercialisation.Using my solid background in the MTB arena, I am uniquely positioned to address the question of "What are the underlying mechanisms impacting on MTB growth and magnetosome formation?" In this project, we will use Mgryph as a MTB model to determine how molecular and metabolic mechanisms impact on growth and magnetosome formation.First, we will characterise the compounds (metabolites) that are key to Mgryph metabolism. We will alter the expression of genes that are related to those compounds and evaluate how these alterations affect Mgryph growth and ability to form magnetosomes. We will also study how iron molecules are transported into Mgryph cells and establish the correlation with magnetosome formation. Our preliminary data shows that both, Mgryph metabolism and the presence of iron inside cells within the same population, presents significant variations. We aim now to further understand the reasons behind our observations and establish links with growth and the formation of magnetosomes. Lastly, we will improve the production of magnetosomes in experiments that resemble industrial settings, that is in bioreactors. We will achieve this by combining the modification of components in the growth media, the use of genetically modified Mgryph and, by developing new production strategies.Together, this knowledge will enable us to enhance the production of magnetosomes, hence increasing their availability for further biomanufacturing and application studies. We will make magnetosomes available to academics and companies interested in their use. This is an essential stage to unlock their full potential as a biotechnology and biomedicine product thus, addressing challenges in health, materials production and sustainability.
今天的经济在很大程度上依赖于石化工业,石化工业为我们提供燃料、化学品和我们社会使用的材料。石油行业每年为英国经济带来约500亿英镑的价值。然而,由于净碳排放对环境的负面影响,这是不可持续的。英国致力于到2050年实现净零碳经济,这意味着我们需要开发替代石油的替代工艺。因此,生物技术提供了巨大的潜力,通过开发更绿色,更清洁的制造工艺和新产品,通过使用活生物体造福社会,对生物经济产生影响,以减缓气候变化。存在一种称为趋磁细菌(MTB)的微生物家族,因为它们可以制造称为磁小体的微小铁晶体,使它们能够像指南针一样发挥作用,并指向地球的磁北极磁小体是“纳米磁体”,由于其有利和独特的性质,可以用作传统化学磁性纳米颗粒(MNP)的创新替代品。它们的应用包括例如癌症治疗、MRI造影剂和金属捕获。因此,磁小体有可能成为下一代的生物MNP使用环境友好的路线生产。然而,磁小体未来的广泛应用将在很大程度上取决于强化高产生物制造的挑战性发展。我们可以使用MTB模型,如Magneto-gryphiswaldense(Mgranus)来应对这一挑战。我们以前已经开发了一种方法来生产和培养磁小体,最近发现,当在空气存在或限制下生长时,磁小体的营养需求显着不同。重要的是,我们还不了解磁小体生产的生物学机制,在Mgranulosa可以提高。这些信息对于开发优化的生物制造和实现磁小体的进一步应用研究和商业化的全部潜力至关重要。利用我在MTB竞技场的坚实背景,我独特地定位于解决“影响MTB生长和磁小体形成的潜在机制是什么?“在这个项目中,我们将使用Mgranulum作为MTB模型来确定分子和代谢机制如何影响生长和磁小体形成。首先,我们将分析Mgranulum代谢的关键化合物(代谢物)。我们将改变与这些化合物相关的基因的表达,并评估这些改变如何影响磁小体的生长和形成磁小体的能力。我们还将研究铁分子如何被转运到磁小体细胞中,并建立与磁小体形成的相关性。我们的初步数据表明,在同一人群中,镁代谢和细胞内铁的存在都存在显着差异。我们现在的目标是进一步了解我们观察背后的原因,并建立与磁小体生长和形成的联系。最后,我们将在类似于工业环境的实验中改进磁小体的生产,即在生物反应器中。我们将通过改变培养基成分、使用转基因磁小体和开发新的生产策略来实现这一目标。这些知识将使我们能够提高磁小体的生产,从而增加其在进一步生物制造和应用研究中的可用性。我们将使磁小体提供给有兴趣使用它们的学术界和公司。这是释放其作为生物技术和生物医学产品的全部潜力的重要阶段,从而应对健康,材料生产和可持续性方面的挑战。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Enhancing students' digital skills through a Biotechnology & Bioprocessing module designed for chemical engineers
通过生物技术提高学生的数字技能
- DOI:10.1080/2331186x.2023.2299201
- 发表时间:2024
- 期刊:
- 影响因子:1.6
- 作者:Fernandez-Castane A
- 通讯作者:Fernandez-Castane A
Valorising Cassava Peel Waste Into Plasticized Polyhydroxyalkanoates Blended with Polycaprolactone with Controllable Thermal and Mechanical Properties
- DOI:10.1007/s10924-023-03167-4
- 发表时间:2024-01-27
- 期刊:
- 影响因子:5.3
- 作者:Martinaud,Emma;Hierro-Iglesias,Carmen;Fernandez-Castane,Alfred
- 通讯作者:Fernandez-Castane,Alfred
An open-source automated magnetic optical density meter for analysis of suspensions of magnetic cells and particles
用于分析磁性细胞和颗粒悬浮液的开源自动磁光密度计
- DOI:10.48550/arxiv.2106.07466
- 发表时间:2021
- 期刊:
- 影响因子:0
- 作者:Welleweerd M
- 通讯作者:Welleweerd M
Evaluation of cell disruption technologies on magnetosome chain length and aggregation behaviour from Magnetospirillum gryphiswaldense MSR-1.
- DOI:10.3389/fbioe.2023.1172457
- 发表时间:2023
- 期刊:
- 影响因子:5.7
- 作者:
- 通讯作者:
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Alfred Fernandez-Castane其他文献
Alfred Fernandez-Castane的其他文献
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