Release date: 2016-08-05
When talking about Chinese scientists working at the Massachusetts Institute of Technology (MIT), the first thing that should come to mind is Zhang Feng, who is engaged in genetic editing research. In fact, there are quite a few Chinese-American talents who have achieved great success at MIT. For example, the one we are going to introduce today, recently in the very promising field of life sciences – synthetic biology – has made a lot of noise. .
He is Timothy K. Lu, a post-80, joined MIT in 2010 and is currently an associate professor at the MIT School of Electrical Engineering and Computer Science and the School of Bioengineering. Lu Guanda, who is only 35 years old this year, has become the head of the MIT Synthetic Biology Research Group. Some people in the industry call him "the thinker in the field of synthetic biology."
Associate Professor Timothy K. Lu
In the late July, the research team led by Lu Guanda published important research papers in Science (1) and Nature News (2). One brings synthetic biology research to another peak (by "programming" E. coli to have a certain "memory ability"); the second synthetic biology invention will bring a lot to the biopharmaceutical industry. Impact.
Speaking of synthetic biology, this year's biggest sensation is the "Human Genome Project-Write" (HGP-write). On June 2, Harvard University geneticist George Church and New York University system geneticist Jef Boeke and other 25 people jointly wrote an article in the journal Science to announce the official launch of HGP-write, which caused a sensation in synthetic biology. extensive attention.
Compared with HGP-write, Lu Guanda's MIT Synthetic Biology Research Group is more realistic. The Lu Guanda team's research in synthetic biology was inspired by electrical engineering and computer science. Inspired by these, they invented new technologies to build "biocircuits" to solve some medical and industrial problems.
In fact, in a previous article "Destroy cancer tissue with the bacteria "death squad", the scientist's invention is simply ingenious", we have introduced the elaborate "biological circuit" designed by Professor Sangeeta Bhatia for cancer treatment. Unlike Professor Bhatia's "biological circuit", which is directly used for treatment, Lu Guanda's "biological circuit" solves the problem of "individualized medicine" in the era of individualized treatment.
Since the US government proposed "precise medical care" last year, the indications for drugs have become more and more detailed. The applicable groups of many drugs are rapidly shrinking. At this rate, it has been developing at a rapid pace. It seems that it will soon be caught from the "beard eyebrows". The way of medication, the era of "individualized medicine" for one person and one medicine. Patients in the era of "individualized medicine" clearly cannot afford the cost of factory-scale large-scale pharmaceuticals. Lu Guanda believes that the problems brought about by this huge change are now going to be solved. Of course, it’s not just Lu Guanda who has this idea.
The loyal readers of Singularity must remember that on May 28th, we wrote that "the pharmaceutical factory was put into the "refrigerator" and the scientists of MIT were stunned...". At that time, three scientists at MIT invented a refrigerator-sized pharmaceutical integration prototype, but this machine is mainly used for synthetic chemical drugs, and it is helpless for the synthesis of protein drugs.
Unexpectedly, after only two months, the problem was solved by the Lu Guanda team at MIT. They used synthetic biology techniques to invent a "micro-bioreactor" through which protein-based drugs (such as peptides, insulin, vaccines, and antibody drugs) needed by patients can be synthesized. At this point, I think MIT scientists seem to have a hard time with the pharmaceutical industry, they seem to want to subvert the traditional pharmaceutical industry.
In fact, the use of biosynthetic technology to produce drugs is nothing new. However, how to meet the demand for drugs in a few patients safely, conveniently and quickly in a micro-reactor is still a big problem. Lu Guanda, who holds a master's degree in engineering from MIT, skillfully solved this problem by using computer science ideas.
The first is to solve the problem of engineering bacteria. Traditional pharmaceutical engineering bacteria are generally only used to produce a drug, and drug synthesis basically does not respond to changes in the external environment. The Lu Guanda team put them in the engineering yeast to produce "biological circuits" that can produce two kinds of drugs. These two "biological circuits" can change the drugs produced according to changes in the surrounding environment.
Life engineering (scientificamerican.com)
When we release some β-estradiol (estrogen) into the environment in which the yeast is grown, the “biological circuit†controlled by β-estradiol is switched on, and the engineered yeast synthesizes a large amount of recombinant human growth hormone. (rHGH, for the treatment of diseases such as growth hormone deficiency in children and adults); if we remove beta-estradiol from the environment, the "biological circuit" controlled by beta-estradiol will be turned off, recombinant human growth hormone The synthesis stops immediately; when we add methanol, the "biological circuit" controlled by methanol is switched on, and the engineered yeast synthesizes a large amount of interferon (a broad-spectrum antiviral agent). This is somewhat similar to the principle of computer work: giving the engineering yeast an instruction, after they accept the instruction, it will complete some sort of process (synthetic drug); when the instruction is cleared, the process ends.
Next, the Lu Guanda team has to design a micro-production process to control the entire production process. In the process, their electrical engineering ideas have helped them a lot. They put a big pharmaceutical factory ingeniously on a microfluidic chip. Due to the complexity of the design, it is not easy to describe in words, I have to follow the schematic diagram step by step.
The upper left corner is the physical map, and the lower right corner is the enlarged schematic (by Qian Qian) [2]
It is not difficult to see from the figure that the left side of the "micro bioreactor" consists of a pipe for injecting liquid, and the right side is the engineering bacteria growth and fermentation liquid filtration zone. The injection unit on the left has 7 holes, 5 in and 2 out; the engineered bacteria and the nutrients for their growth and the chemicals that induce their synthesis are piped into the reactor on the right.
The right reactor consists of polycarbonate and a gas permeable silicone rubber membrane. The oxygen in the air can enter freely. There are also oxygen sensors and pH sensors on the reactor for detecting internal environmental conditions. When we need to make engineering bacteria produce another In a medicine, the reactor is washed away by slowly injecting nutrients, and the engineered bacteria are intercepted by the filter, and then retained in the reactor, and then the corresponding inducing substance is injected.
The prototype of the "micro bioreactor", the whole machine is like a circuit board. As can be seen from the top schematic, methanol and β-estradiol are the switches of the entire circuit [2]
According to Lu Guanda, the FDA has approved more than 500 protein drugs produced in engineered yeast, including peptides, enzymes, hormones and monoclonal antibodies. At present, the "micro bioreactor" invented by the Lu Guanda team can synthesize the two protein drugs described above. Of course, this is only a preliminary study, and their goal is that an engineered strain can synthesize multiple drugs. In this way, the use value of this "micro bioreactor" will be greatly improved.
As for the application scenario of this "micro-bioreactor", the US Defense Advanced Research Projects Agency (DARPA), which supports the Lu Guanda team to do research, has different views from Lu Guanda. DARPA values ​​the fact that this study can be used for in-situ production of field drugs, which is the same starting point as DARPA supports another pharmaceutical "refrigerator". However, this does not prevent the Lu Guanda team from contributing to the original intention of individualized treatment. In addition, this study has considerable value for the supply of drugs in remote and backward areas.
According to Lu Guanda, a large part of his innovative spirit of innovation is from his father. In the 1970s, Lu Guanda's father went to Stanford to study. Later, he participated in semiconductor-related R&D work at IBM, and finally returned to Taiwan to start a business and founded an integrated circuit company. In 1999, Lu Guanda went to the United States to study. He majored in electronic engineering at MIT and Harvard. Later, he studied under the leadership of synthetic biology, Professor Jim Collins, and obtained a doctorate in biomedical sciences. In 2010, Lu Guanda, 29, was named one of the "35 Global Innovation Youths" by the MIT Science and Technology Magazine.
Lu Guanda has participated in the establishment of several companies, including Sample6, Eligo Biosciences and Synlogic. Synlogic was founded in 2014 by Lu Guanda and his doctoral tutor Jim Collins. Synlogic is a synthetic biology company that carries Lu Guanda's dream. As of the date of publication, Synlogic has six drugs under study.
Synlogic's 6 drugs, indications and research progress (Synlogic's official website)
Lu Guanda’s experience is somewhat inspiring for Chinese students who are studying in Europe and the United States. Under the scientific and educational environment of European and American knowledge, we should not focus on only one area, but should pay attention to the development of interdisciplinary subjects. After all, the progress in many fields now depends on the mutual integration of various disciplines.
Reference material
[1]Roquet N, Soleimany AP, Ferris AC, Aaronson S, Lu TK. 2016. Synthetic recombinase-based state machines in living cells. Science 353
[2] Perez-Pinera P, Han N, Cleto S, Cao J, Purcell O, et al. 2016. Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care. Nat Commun 7
Source: Singularity Network
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