STTR Phase I: Protease-based purification of recombinant human matrix metalloproteases

STTR 第一阶段：基于蛋白酶的重组人基质金属蛋白酶纯化

• 批准号: 2001749
• 负责人: SUMAER KAMBOJ
• 金额: $ 22.5万
• 依托单位: SARKAR-KLEIN-LABS
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2001749&HistoricalAwards=false
• 关键词: STTR; Phase; Protease; based; purification

The broader impact of this Small Business Technology Transfer (STTR) Phase I project is an enabling technology to improve research into many diseases. This STTR project will develop human matrix metalloprotease (MMPs), a class of enzymes that degrade many biomolecules including collagen, the most abundant structural protein in the human body. MMPs are critical for numerous normal and pathological processes, such as tumor growth. However, MMPs are expensive to produce, and researchers need a reliable source of well-characterized human MMPs so that researchers can pursue high quality, reliable experiments on basic science and medical applications. Furthermore, this project can impact other fields that use enzymes, such as the food industry, renewable energy, and human health.The proposed project will commercialize inexpensive recombinant human MMPs produced in E. coli. MMPs degrade and regulate various structural components of the extracellular matrix (ECM), impacting pathologies such as metastasis of solid tumors, which cannot occur without MMP-mediated degradation of collagens. Recombinant MMPs can support this research. This STTR project will advance development of protease-based protein purification without chromatography, enabling rapid and low-cost purification. The technical R&D tasks include developing technical assessments for MMPs. The technical assessments will contain raw and curated data for purity, identity, concentration, and activity of MMPs at different solution conditions. This project will investigate development of MMPs as anti-biofilm and anti-clot agents beyond the traditional collagen degradation field of research. The protease-based method used to obtain MMPs can be used to purify other proteins as well. MMPs also have biotechnological applications in broad-spectrum degradation of tissue components for cell isolation from tissue samples and diseases involving aberrant collagen depositions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业技术转让（STTR）第一阶段项目的更广泛影响是一种能够改善许多疾病研究的技术。 该STTR项目将开发人类基质金属蛋白酶（MMPs），这是一类降解许多生物分子的酶，包括胶原蛋白，胶原蛋白是人体中最丰富的结构蛋白。MMPs对于许多正常和病理过程（例如肿瘤生长）是至关重要的。然而，MMPs的生产成本很高，研究人员需要可靠的表征良好的人类MMPs来源，以便研究人员可以在基础科学和医学应用方面进行高质量，可靠的实验。此外，该项目还将影响食品工业、可再生能源和人类健康等其他使用酶的领域。杆菌MMP降解和调节细胞外基质（ECM）的各种结构组分，影响病理学，如实体瘤的转移，其在没有MMP介导的胶原降解的情况下不能发生。重组MMPs可以支持这项研究。 该STTR项目将推进基于蛋白酶的蛋白质纯化的开发，而无需色谱，从而实现快速和低成本的纯化。技术研发任务包括为MMPs开发技术评估。技术评估将包含不同溶液条件下MMP的纯度、鉴别、浓度和活性的原始和精选数据。本项目将研究MMPs作为抗生物膜和抗凝血剂的发展，超越传统的胶原蛋白降解研究领域。用于获得MMP的基于蛋白酶的方法也可用于纯化其他蛋白质。MMPs在广谱降解组织成分方面也有生物技术应用，用于从组织样本和涉及异常胶原沉积的疾病中分离细胞。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。