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A bio-NanoRobot Design for Drosophila Therapeutic Cloning

机译:用于果蝇治疗性克隆的bio-NanoRobot设计

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To investigate Somatic Cell Nuclear Transfer (SCNT), we choose the Drosophila cloning based on a recent experiment (Haigh, MacDonald, Lioyd, Gen. V. 169,1165, 2005) to be improving the adulthood rate in 2-week turn-around time. Original 1% success rate might be due to three less certain key steps: (ⅰ) The double membranes of a nucleus has at its pore led to the attached Rough Endoplasmic Reticulum (ER), passing the genetic instruction to assemble amino acids, proteins and lipid at its smooth end. Also, any mismatch of nucleus with mitochondria (MT) having own small genome for energy production had led to reprogramming failure. (D. Wallace, UC Irvine, Nature, Vol. 439, pp.653). We ask "whether a guest DNA shall come with its servants, ER, MT, etc or not." It seemed to be logical to have a whole package replaced the embryonic host cell, equipped with all housekeeping, energy production and mitosis functionalities except the genetic information. To answer this hypothesis, we design a bio-NanoRobot having a surgical precision in removing the desired nucleus with or without its attached ER and MT material. The design is based on a real-time multiplexing principle of combining both the soft-contact-vision of the Nobel Laureate Binning called Atomic Force Microscope (AFM) and the hard-grasp-action called NanoRobot™ by Xi and Szu, 2004. However, applying it, we must re-design a new bio-NanoRobot, consisting of two parts: (a) multiple resolution analysis (MRA) using AI to control a dual-resolution vision system: the soft-contact-vision AFM co-registered with a on-contact high resolution imaging; and (b) two cantilever arms capable to hold and enucleate a cell. The calibration and automation are controlled by AI Case-Based reasoning (CBR) together with AI Blackboard (BB) of the taxonomy, necessary for integrating different tool''s tolerance and resolution at the same location. Moreover, keeping the biological sample in one place, while a set of tools rotates upon it similar to a set of microscopic lenses, we can avoid the non-real-time re-imaging, and inadvertent contamination. Applying an imposing electrical field, we can take the advantage of structure differences in smooth nuclear membranes inducing Van der Waal''s forces versus random cytoplasm, (ⅱ) The re-programming of transplanted cells to the ground state is unclear and usually relies on electrochemical means tested systematically in a modified 3D Caltech micro-fluidics. (ⅲ) Our real-time MRA video-manipulator can elucidate the mitosis''s tread-mill assembly mechanism in the development course of pluripotent stem cell differentiation into specialized tissue cell engineering. Such a combination bio-NanoRobot and micro-fluidic massive parallel assembly-line approach might not only replace the aspirating pipette with a self- enucleating Drosophila embryonic eggs, but also genetically reproduce a large amount of cloning embryonic eggs repeatedly for various re-programming hypotheses.
机译:为了研究体细胞核移植(SCNT),我们基于最近的一项实验(Haigh,MacDonald,Lioyd,Gen​​。V. 169,1165,2005)选择果蝇克隆,以提高两周周转期的成年率。时间。最初的1%成功率可能是由于以下三个关键步骤较少:(ⅰ)核的双膜在其孔中导致附着的粗面内质网(ER),并通过了遗传指令来组装氨基酸,蛋白质和脂质在其平滑末端。同样,任何核与具有自身小基因组以产生能量的线粒体(MT)的错配都会导致重新编程失败。 (D.Wallace,UC Irvine,自然,第439卷,第653页)。我们问“客人的DNA是否应随其仆人,ER,MT等一起出现”。完整的包装代替胚胎宿主细胞似乎很合乎逻辑,该宿主细胞具备除遗传信息外的所有管家,能量生产和有丝分裂功能。为了回答这个假设,我们设计了一种具有手术精度的bio-NanoRobot机器人,可在有或没有其ER和MT材料的情况下去除所需的核。该设计基于实时多路复用原理,该原理结合了诺贝尔奖获得者Binning的软接触式视觉(称为原子力显微镜(AFM))和Xi- and Szu,2004年的称为NanoRobot™的硬式捕捉动作。 ,要应用它,我们必须重新设计一个新的生物纳米机器人,它由两部分组成:(a)使用AI来控制双分辨率视觉系统的多分辨率分析(MRA):共同注册的软接触式视觉AFM具有接触式高分辨率成像; (b)两个能够支撑和摘除细胞的悬臂。校准和自动化由基于案例的AI案例推理(CBR)和分类法的AI Blackboard(BB)进行控制,这对于在同一位置集成不同工具的公差和分辨率是必需的。此外,将生物样品放置在一个地方,同时使用一组工具类似于一组显微镜头在其上旋转,我们可以避免非实时重新成像和无意的污染。施加强加的电场,我们可以利用平滑核膜诱导范德华力与随机细胞质的结构差异(ⅱ)将移植细胞重编程为基态尚不清楚,通常依赖于电化学方法在改良的3D Caltech微流体中进行了系统测试。 (ⅲ)我们的实时MRA视频操纵器可以在多能干细胞分化为专门的组织细胞工程的发展过程中阐明有丝分裂的跑步机装配机制。这种将生物纳米机器人和微流体大规模并行装配线方法相结合的方法,不仅可以用自去核的果蝇胚胎卵代替吸移管,而且可以通过遗传方式重复复制大量克隆的卵,以用于各种重新编程的假设。 。

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