5 challenges we could solve by designing new proteins | David Baker

5 challenges we could solve by designing new proteins | David Baker


I’m going to tell you about the most
amazing machines in the world and what we can now do with them. Proteins, some of which you see inside a cell here, carry out essentially all the important
functions in our bodies. Proteins digest your food, contract your muscles, fire your neurons and power your immune system. Everything that happens in biology — almost — happens because of proteins. Proteins are linear chains
of building blocks called amino acids. Nature uses an alphabet of 20 amino acids, some of which have names
you may have heard of. In this picture, for scale,
each bump is an atom. Chemical forces between the amino acids
cause these long stringy molecules to fold up into unique,
three-dimensional structures. The folding process, while it looks random, is in fact very precise. Each protein folds
to its characteristic shape each time, and the folding process
takes just a fraction of a second. And it’s the shapes of proteins which enable them to carry out
their remarkable biological functions. For example, hemoglobin has a shape
in the lungs perfectly suited for binding a molecule of oxygen. When hemoglobin moves to your muscle, the shape changes slightly and the oxygen comes out. The shapes of proteins, and hence their remarkable functions, are completely specified by the sequence
of amino acids in the protein chain. In this picture, each letter
on top is an amino acid. Where do these sequences come from? The genes in your genome
specify the amino acid sequences of your proteins. Each gene encodes the amino acid
sequence of a single protein. The translation between
these amino acid sequences and the structures
and functions of proteins is known as the protein folding problem. It’s a very hard problem because there’s so many different
shapes a protein can adopt. Because of this complexity, humans have only been able
to harness the power of proteins by making very small changes
to the amino acid sequences of the proteins we’ve found in nature. This is similar to the process
that our Stone Age ancestors used to make tools and other implements
from the sticks and stones that we found in the world around us. But humans did not learn to fly
by modifying birds. (Laughter) Instead, scientists, inspired by birds,
uncovered the principles of aerodynamics. Engineers then used those principles
to design custom flying machines. In a similar way, we’ve been working for a number of years to uncover the fundamental
principles of protein folding and encoding those principles
in the computer program called Rosetta. We made a breakthrough in recent years. We can now design completely new proteins
from scratch on the computer. Once we’ve designed the new protein, we encode its amino acid sequence
in a synthetic gene. We have to make a synthetic gene because since the protein
is completely new, there’s no gene in any organism on earth
which currently exists that encodes it. Our advances in understanding
protein folding and how to design proteins, coupled with the decreasing cost
of gene synthesis and the Moore’s law increase
in computing power, now enable us to design
tens of thousands of new proteins, with new shapes and new functions, on the computer, and encode each one of those
in a synthetic gene. Once we have those synthetic genes, we put them into bacteria to program them to make
these brand-new proteins. We then extract the proteins and determine whether they function
as we designed them to and whether they’re safe. It’s exciting to be able
to make new proteins, because despite the diversity in nature, evolution has only sampled a tiny fraction
of the total number of proteins possible. I told you that nature uses
an alphabet of 20 amino acids, and a typical protein is a chain
of about 100 amino acids, so the total number of possibilities
is 20 times 20 times 20, 100 times, which is a number on the order
of 10 to the 130th power, which is enormously more
than the total number of proteins which have existed
since life on earth began. And it’s this unimaginably large space we can now explore
using computational protein design. Now the proteins that exist on earth evolved to solve the problems
faced by natural evolution. For example, replicating the genome. But we face new challenges today. We live longer, so new
diseases are important. We’re heating up and polluting the planet, so we face a whole host
of ecological challenges. If we had a million years to wait, new proteins might evolve
to solve those challenges. But we don’t have
millions of years to wait. Instead, with computational
protein design, we can design new proteins
to address these challenges today. Our audacious idea is to bring
biology out of the Stone Age through technological revolution
in protein design. We’ve already shown
that we can design new proteins with new shapes and functions. For example, vaccines work
by stimulating your immune system to make a strong response
against a pathogen. To make better vaccines, we’ve designed protein particles to which we can fuse
proteins from pathogens, like this blue protein here,
from the respiratory virus RSV. To make vaccine candidates that are literally bristling
with the viral protein, we find that such vaccine candidates produce a much stronger
immune response to the virus than any previous vaccines
that have been tested. This is important because RSV
is currently one of the leading causes of infant mortality worldwide. We’ve also designed new proteins
to break down gluten in your stomach for celiac disease and other proteins to stimulate
your immune system to fight cancer. These advances are the beginning
of the protein design revolution. We’ve been inspired by a previous
technological revolution: the digital revolution, which took place in large part
due to advances in one place, Bell Laboratories. Bell Labs was a place with an open,
collaborative environment, and was able to attract top talent
from around the world. And this led to a remarkable
string of innovations — the transistor, the laser,
satellite communication and the foundations of the internet. Our goal is to build
the Bell Laboratories of protein design. We are seeking to attract
talented scientists from around the world to accelerate the protein
design revolution, and we’ll be focusing
on five grand challenges. First, by taking proteins from flu strains
from around the world and putting them on top
of the designed protein particles I showed you earlier, we aim to make a universal flu vaccine, one shot of which gives a lifetime
of protection against the flu. The ability to design — (Applause) The ability to design
new vaccines on the computer is important both to protect
against natural flu epidemics and, in addition, intentional
acts of bioterrorism. Second, we’re going far beyond
nature’s limited alphabet of just 20 amino acids to design new therapeutic candidates
for conditions such as chronic pain, using an alphabet
of thousands of amino acids. Third, we’re building
advanced delivery vehicles to target existing medications
exactly where they need to go in the body. For example, chemotherapy to a tumor or gene therapies to the tissue
where gene repair needs to take place. Fourth, we’re designing smart therapeutics
that can do calculations within the body and go far beyond current medicines, which are really blunt instruments. For example, to target a small
subset of immune cells responsible for an autoimmune disorder, and distinguish them from the vast
majority of healthy immune cells. Finally, inspired by remarkable
biological materials such as silk, abalone shell,
tooth and others, we’re designing new
protein-based materials to address challenges in energy
and ecological issues. To do all this,
we’re growing our institute. We seek to attract energetic,
talented and diverse scientists from around the world,
at all career stages, to join us. You can also participate
in the protein design revolution through our online
folding and design game, “Foldit.” And through our distributed
computing project, [email protected], which you can join from your laptop
or your Android smartphone. Making the world a better place
through protein design is my life’s work. I’m so excited about
what we can do together. I hope you’ll join us, and thank you. (Applause and cheers)


100 thoughts on “5 challenges we could solve by designing new proteins | David Baker

  1. Hi, I am a woman who reads book in Canada, this is very interesting topic for all of us.

  2. Being a pediatric RN for the last 30 years I have pioneered through the technologies we see today. I have seen many babies die of RSV and influenza. how nice it would be to have RSV and Flu Irradicated before I retire. I am excited to see the future of medicine. I hope to see a cure for cancer before it is my turn to get it.

  3. This is the most amazing thing I've ever heard of. Simply astonishing. Designer proteins will do so much new weird and jaw-dropping things. Holy crap.

  4. I sometimes worry that protein patents will thwart progress. Hopefully, there will be many competing proteins that can do the same job.

  5. Just read this morning about incredible advances google deepmind has made in protein folding and how they maybe able to challenge big pharma; naturally this inspiring video popped up in recommendations. Of course I was the 23rd commenter

  6. A humanidade está chegando em um novo patamar, e isso me faz muito feliz!

    Imaginem onde estaremos daqui a 30 anos, o tanto de avanços que já existirão em todas as áreas da humanidade! É lindo!

  7. A piece of cake from Baker. I wish everybody get enjoyed with my Arabic subtitles when be approve and published.

  8. Think about the advancement and achievements that could be accomplished with unlimited access to the patent system

  9. The problem with short term changes are the unforeseen long range consequences. Growth harmonies given to livestock, chickens, etc., have lowered the age of puberty in humankind and this is a readily confirmable statistic. While genetic manipulation of food stock has not had time for truly long term studies to be preformed, even the short term research indicates disturbing anomalies which could become troubling to future generations. Unfortunately, quick profit dictates immediate procedure and questions of future consequence are left for future generations to worry about. So, alter DNA to prevent lung disease, and discover over time that it has lowered human fertility, or intelligence, or immuno response, or any number of other possible disastrous consequence. I do not say that such research is bad, only that we need to better know and understand what we tinker with, i.e. DNA and genetics, before we attempt to "fix" it. We have only recently come to reasonably map the human genome and we have no idea of the intricacies of their interactions. If you're not sure how it actually works, how can you change some portion of it with anything like reasonable assurance over long term results?

  10. Baker's lab is the entire reason why I'm transferring to UW. Being able to participate with some of the greatest scientists on groundbreaking and paradigm-crushing breakthroughs is honestly my only aspiration. This lab is going to help usher in a new age of human prosperity and I'm psyched to be able to live through it.

  11. I'd love to see if this type of technology could be paired with algorithm technology that's still in development today. While it's still in the realm of sci-fi right now, I love the idea of a protein that could study virus or bacterial behaviors and evolution. Like David said, it will end up being a lifetime vaccine that self-develops to fight pathogens.

  12. Genetic Engineering will be one of the top 10 reasons in my list.. of how mankind destroys itself, but hey, don't let the movie "LEGEND" be a warning of course.

  13. You could also create new prions that could wipe out mankind or even all life on Earth. How would you ever know. Not enough is know about what can go wrong. "Nature will find a way".
    https://en.wikipedia.org/wiki/Prion

  14. Targeted chemotherapy through protein informatics will revolutionize post surgical cancer treatments. Chemotherapy are so painful, and the patient suffers a lot. If it is targeted, half the pain, twice the gains!

  15. If cyborg 🕵️‍♀️ flesh and other
    Its good for all organic organisms
    Not just humans
    Horizontal Bubba

  16. We live in a world with so many questions with no answers that we must to appreciate and ask for our government to invest in researches. It’s so many diseases, it’s so many people dying without adequate treatment, we deserve a better future to our health!

  17. But how will synthetic proteins affect the natural proteins and lifeforms in nature? Surely something will change if we choose to spread synthetic proteins around the world to solve problems like pollution.

    I wonder if we really could speed up evolution this way?

  18. Hello , i can translate your all videos into Arabic to spread your videos and spread knowledge for each video i will take only 1$ . I think it will be good for you.

  19. As the data set may be sufficient to advance more about the options in the world, we do not do the work because people have money and they can invest in it, they just do not invest. Nowadays, for example, people who are hungry, but not for lack of food, but people who have money or the big producers of food, it does not matter who is hungry.

  20. I love the open honor system in the research on proteins. Anyone is allowed to participate, as demonstrated by the apps that have been created for the world to use. I remember when I took a certified nursing assistant course (the lowest level of the nursing field), and when they taught us about the protein shapes I was just so immediately drawn to their aesthetic, structure, and function. It really wasn’t so difficult to learn the basics.

  21. Congratulations to u sir and your team that make protein designing real. I have a query. By Designing protein under your program [email protected], can one claim for intellectual property for it???

  22. OMG, This is Awesome, David. Thanks for bringing your ideas with so many clarity and naturalness. I loved the 3d representations of proteins and amino acids, looks great imagine trillions and trillions of things like that in our body.

    The idea of create peptides is so interesting, but so complex. However, I have hope in a future guided by science, and also that all of this can be normal in future, helping people and improving our power as humans.

    My favourite part was your quote: …Bring biology out of stone age to a technological revolution… As a biology student, this quote gave me "positive goosebumps", and inspiration to proceed in the science way! Thanks!

  23. Now we just need to resolve P vs NP so we know whether or not there is a way to do these computations in polynomial time.

  24. Awesome ! The advance of biology and computing is very important to the future of prevention of diseases.
    The proteins are essentials to create lifetime vaccines.

  25. When I was learning about proteins in biology class I thought “screw nanotechnology, let’s explore what we can do with proteins.” Boom! Didn’t know somebody was onto this!

  26. While I liked the talk, I thought it was a little short and very surface level. I wanted to hear about how they were actually designing proteins. As somebody who works in molecular biology, I get the sense that protein folding is still very much a mystery, and that the flu vaccine stuff is mostly just fusing proteins that already exist in nature (biological "stone age" technology as he called it). The extended alphabet stuff is very cool and I have read the literature, but he didn't go into any of the details here.

  27. This is very insightful as well as optimistic – I hope to see interest in protein synthesis grow considering its astronomical potential to change our world

  28. The third video is amazing! I have studied a lot about this, in the sense that I have curricular components like immunology, biology and biochemistry that stimulate this. Proteins are amazing and science, despite my many criticisms, is also.
    My favorite part of the video is when amino acids appear to form proteins, still early on. it's pretty cool how something specific can revolutionize the world, but I think it's going to take a lot of time, especially on smart cancer therapy.
    Finally, I think it's worth seeing something about enzymes too, and that fits the theme.

  29. I am an undergrad student pursuing Biological Engineering major. I hope I get a chance to intern under this magical protein man

  30. Nice that he advertised the 2 projects where people can help at the end. But both foldit and [email protected] had horrible websites that made me feel uncomfortable. Also I didn't find any source code to the tools in 10 minutes searching. Cool idea but pointless how it is currently implemented. If there was a nice and legit link to source code and clean build intructions and a more motivating design i would probably run some of the software but not like this.

  31. The video is really interesting, an important advance, but I think because it's a subject that I don't have such affinity sometimes it was difficult to understand what was being said or even to concentrate.

  32. In 1998 I worked with a professor Gustavo Arteca, Laurentian University, who was trying to find a mathematical formula to predict protein folding from a random Amino Acid chain…. This is the future Gustavo told me back then to design proteins that go after the bad proteins…. At the time, computers could emulate a nuclear blast but computers could not predict protein folding… This video brought back memories of the very small part I played in this research area…

  33. Knowing how science organizes itself to solve the world's problems is very interesting and inspires other professionals and scholars in the field to contribute as well. Understanding how the world around us is scientifically important is important for us to be aware of the way things work. Imagine the changes that can happen in the world from the advance of science is wonderfull and motivating for humanity to move on.

  34. I am counting on #4 smart therapeutics to cure autoimmune dysfunction. it is causing so much discomfort to people that there is no cure to it.

  35. Just imagine.. our lifes will be completely different in the future. I hope that new medicine will decide all diseases and let people live cool.

  36. Finally some amazing science on ted again….makes great watching…..especially instead of all the social warrior bull crap…

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