3 ms·

While I definitely agree that the software around synthetic biology is weak, I think this is not actually the problem bottlenecking the field. Ultimately, most

While I definitely agree that the software around synthetic biology is weak, I think this is not actually the problem bottlenecking the field. Ultimately, most efforts in synthetic biology are gated foremost by a lack of underlying biological knowledge. Automation may aid discovery, but the number of components and complexity of biological systems leaves many unanswered questions. Yes, There have been demonstrators of biological computing and circuits, but from a functional perspective they are extremely limited, especially compared to in vivo systems. Put a different way, even if we can do complex "computation" in a cell, our understanding of the "I/O" is too superficial to design systems to treat diseases or act as devices. The failure of rational drug design over the last 20 years has taught the pharmaceutical community this lesson quite harshly. Understanding the interfaces and mechanisms that our "biological computers" will work with will require more research in fields like structural and molecular biology, and this work will take time. With that said, there are some useful systems we can engineer in the meantime; for example, biosynthesis pathway work is well underway. Just realize that these systems don't require substantial engineered computation.

dnautics 13y ago
> While I definitely agree that the software around synthetic biology is weak, I think this is not actually the problem bottlenecking the field. Ultimately, most efforts in synthetic biology are gated foremost by a lack of underlying biological knowledge. This is spot-on correct. In the lab I worked in, we are working on a gene cluster of 11 genes, that result in the assembly of an enzyme that creates hydrogen. The PI's project was to play around with "promoters" that tell the bacterium to produce the genes. Think of this as 'script kiddie' work. I came in and immediately told him that this was the wrong approach; we had to alter the structure and chemistry of the enzymes themselves (think of this as 'assembler-level hacking'). Thankfully he was sympathetic to my argument and let me play around; I achieved a 3x improvement in enzyme activity. This summer,we tested the original idea, and all of the variants we tested were worse than what we started out. Also, and this is my highly opinionated position informed by my experience as the sole chemist in a synthetic biology lab, but part of the problem is that a lot of biologists tracked themselves into biology because they didn't do so hot at chemistry. Many synthetic biology problems are chemistry problems, and even problems that are not on first blush like those that Drew Endy are trying to solve really become easy to grok if you're used to thinking qualitatively in terms of statistical thermodynamics and can mentally estimate collisions per nanosecond, from concentrations and kinetic parameters. These are quintessentially chemistry skills. reference: https://www.ncbi.nlm.nih.gov/pubmed/23819621 https://www.ncbi.nlm.nih.gov/pubmed/23819621
- spartango 13y ago
  Coming from the world of biophysics and structural bio, I wholeheartedly agree. Multidisciplinary approaches answer many more questions, but can be quite challenging to wrap your head around. Thinking like this is awesome when it happens: a lab I worked in would combine structures of motor proteins with single molecule studies, targeted mutation work, and even in-vivo studies. The result? You could take specific loops and helices within the motor and not only understand where and how they interact with a microtubule, but also how that affected the motor's mechanical action and cellular behavior. http://www.ncbi.nlm.nih.gov/pubmed/22997337 http://www.ncbi.nlm.nih.gov/pubmed/22997337
  - dnautics 13y ago
    No. It's not about thinking multidisciplinary. Often times multidisciplinary translates to, "half-assed everything". What I am saying is you have to be able to physically do the basics in everything. And modestly well. There is nothing, nothing that tempers the brain like experiential knowledge. For chemistry, the basic skills include: reading an NMR, looking at a mechanism and say, that makes no sense, running a silica gel column, shooting something down a mass spec... For biology, that's designing an analytical PCR from scratch, cloning (knowing the difference between a K12 and B strain, for example), doing western blots. And you better be able to tell me the chemical, protein structural, and enzyme mechanism differences between arginine and lysine without looking it up - I remember knowing biophysicists who couldn't do that - I remember PhDs who get their training in ostensibly multidisciplinary labs who couldn't do a single thing on that list. Hell, one of them is a Professor at UW Seattle; when he went off to do his postdoc he was scared out of his pants because he went into a yeast lab without knowing how to clone anything because the tech did all of it for him in grad school. Another real problem is we don't teach students anything anymore on the premise that there's too much to know, and as long as you can look it up, it will be fine. Or if you are working interdisciplinarily, your colleague will be able to tell you (of course they're relying on you too so there's a bootstrapping problem). This is terrible. Sometimes you need to call someone on their bullshit, say during a lecture, or even more importantly during a meeting where actionable decisions are being made and critical insight can avoid wasting time and effort. If you don't have a significant depth of knowledge, which multidisciplinarity typically doesn't encourage - because it's hard - you are just a body making warmth in that room. You need to have instant recall of as much related information as possible at all times when doing science.

dnautics 13y ago

> While I definitely agree that the software around synthetic biology is weak, I think this is not actually the problem bottlenecking the field. Ultimately, most efforts in synthetic biology are gated foremost by a lack of underlying biological knowledge. This is spot-on correct. In the lab I worked in, we are working on a gene cluster of 11 genes, that result in the assembly of an enzyme that creates hydrogen. The PI's project was to play around with "promoters" that tell the bacterium to produce the genes. Think of this as 'script kiddie' work. I came in and immediately told him that this was the wrong approach; we had to alter the structure and chemistry of the enzymes themselves (think of this as 'assembler-level hacking'). Thankfully he was sympathetic to my argument and let me play around; I achieved a 3x improvement in enzyme activity. This summer,we tested the original idea, and all of the variants we tested were worse than what we started out. Also, and this is my highly opinionated position informed by my experience as the sole chemist in a synthetic biology lab, but part of the problem is that a lot of biologists tracked themselves into biology because they didn't do so hot at chemistry. Many synthetic biology problems are chemistry problems, and even problems that are not on first blush like those that Drew Endy are trying to solve really become easy to grok if you're used to thinking qualitatively in terms of statistical thermodynamics and can mentally estimate collisions per nanosecond, from concentrations and kinetic parameters. These are quintessentially chemistry skills. reference: https://www.ncbi.nlm.nih.gov/pubmed/23819621 https://www.ncbi.nlm.nih.gov/pubmed/23819621

spartango 13y ago
Coming from the world of biophysics and structural bio, I wholeheartedly agree. Multidisciplinary approaches answer many more questions, but can be quite challenging to wrap your head around. Thinking like this is awesome when it happens: a lab I worked in would combine structures of motor proteins with single molecule studies, targeted mutation work, and even in-vivo studies. The result? You could take specific loops and helices within the motor and not only understand where and how they interact with a microtubule, but also how that affected the motor's mechanical action and cellular behavior. http://www.ncbi.nlm.nih.gov/pubmed/22997337 http://www.ncbi.nlm.nih.gov/pubmed/22997337
- dnautics 13y ago
  No. It's not about thinking multidisciplinary. Often times multidisciplinary translates to, "half-assed everything". What I am saying is you have to be able to physically do the basics in everything. And modestly well. There is nothing, nothing that tempers the brain like experiential knowledge. For chemistry, the basic skills include: reading an NMR, looking at a mechanism and say, that makes no sense, running a silica gel column, shooting something down a mass spec... For biology, that's designing an analytical PCR from scratch, cloning (knowing the difference between a K12 and B strain, for example), doing western blots. And you better be able to tell me the chemical, protein structural, and enzyme mechanism differences between arginine and lysine without looking it up - I remember knowing biophysicists who couldn't do that - I remember PhDs who get their training in ostensibly multidisciplinary labs who couldn't do a single thing on that list. Hell, one of them is a Professor at UW Seattle; when he went off to do his postdoc he was scared out of his pants because he went into a yeast lab without knowing how to clone anything because the tech did all of it for him in grad school. Another real problem is we don't teach students anything anymore on the premise that there's too much to know, and as long as you can look it up, it will be fine. Or if you are working interdisciplinarily, your colleague will be able to tell you (of course they're relying on you too so there's a bootstrapping problem). This is terrible. Sometimes you need to call someone on their bullshit, say during a lecture, or even more importantly during a meeting where actionable decisions are being made and critical insight can avoid wasting time and effort. If you don't have a significant depth of knowledge, which multidisciplinarity typically doesn't encourage - because it's hard - you are just a body making warmth in that room. You need to have instant recall of as much related information as possible at all times when doing science.