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Erica Saphire’s tiny world
La Jolla Institute for Immunology lays out the first-ever structure of the entire human antibody
Dr. Erica Saphire handles the enemy. Revolutionary microscopes enable details.
Take two Titan Krios microscopes, a whole lot of viruses, and a sharp scientist, and you have full-on war against immune-disease.
I’m still in the thrall of this local research tank which is looking into the immune response of people to dangerous diseases like Dengue and Alzheimer’s. (See previous Golden Dreams item: “La Jolla Institute for Immunology studies the effects of Alzheimer’s in Women,” published 2/3/23.) How could I not be? LJII, near the UCSD campus, has ended up laying out the first-ever structure of the entire human antibody, under the direction of Erica Ollman Saphire. Her lab now leads the world in finding out how to fight hellish critters like the Ebola, Sudan, Marburg, Bundibugyo and Lassa viruses — as well as making inroads into Alzheimer’s and Parkinson’s diseases.
The achievement is all the more amazing when you consider that this wasn’t always her scientific dream. Just the opposite: “I was going to go to graduate school to study marine biology,” says Professor Safire. “And I had this idea of bridging one of the sequences. As a biochemistry major at Rice, I was required to take molecular biophysics. I saved that for the very last semester because I was fairly certain I was going to flunk this course, and I didn’t want the ‘F’ to be on my graduate school transcript. But I had already decided, ‘I’m going to suffer through this terrible course that has been prescribed to me.’”
And then: eureka. “From the very first day, I loved it. I remember the exact day, even the chair I was sitting in, in the lecture hall, when the professor explained to me that by using X-rays, and the scattering of the X-rays, one could mathematically calculate a topographical map of the location of every electron in a protein, and how much it moved from that position. And you could see a thing which was sub-microscopic. It was like the clouds parting, and light came out. That was what I wanted to do with the rest of my life, because it was the most intellectually exciting thing I had ever heard, that if you could write down the set of mathematical equations, the set of molecular structure of something, and how it’s folded, and how if this mine of information got knit into a three-dimensional moving structure of a machine, you could write down and calculate anything you would need to know about the function of that molecule. It should be written in that structure. That was what I was going to do: I was going to reveal these structures. So we did!”
She holds up a blue and yellow model of a tiny virus. “This is a piece of the inner workings of a Lassa virus, and this, in the center, in purple, orange and green, is the surface protein. This is the molecule it uses to attach to a human cell and drive it in. What we’re showing you here are antibodies, and each one [that] has a hole in it is a different antibody, [which we collected] from a human survivor from villages in Sierra Leone and Nigeria. You’re looking at and holding how these humans have survived this virus.”
I don’t fully understand what I’m looking at, but I do know that it is remarkable, and that this remarkable woman’s love affair with some of the greatest killers on the planet may save us all from becoming future statistics.
Here's something you might be interested in.
Erica Saphire’s tiny world
La Jolla Institute for Immunology lays out the first-ever structure of the entire human antibody
Erica Saphire’s tiny world
La Jolla Institute for Immunology lays out the first-ever structure of the entire human antibody
Dr. Erica Saphire handles the enemy. Revolutionary microscopes enable details.
Take two Titan Krios microscopes, a whole lot of viruses, and a sharp scientist, and you have full-on war against immune-disease.
I’m still in the thrall of this local research tank which is looking into the immune response of people to dangerous diseases like Dengue and Alzheimer’s. (See previous Golden Dreams item: “La Jolla Institute for Immunology studies the effects of Alzheimer’s in Women,” published 2/3/23.) How could I not be? LJII, near the UCSD campus, has ended up laying out the first-ever structure of the entire human antibody, under the direction of Erica Ollman Saphire. Her lab now leads the world in finding out how to fight hellish critters like the Ebola, Sudan, Marburg, Bundibugyo and Lassa viruses — as well as making inroads into Alzheimer’s and Parkinson’s diseases.
The achievement is all the more amazing when you consider that this wasn’t always her scientific dream. Just the opposite: “I was going to go to graduate school to study marine biology,” says Professor Safire. “And I had this idea of bridging one of the sequences. As a biochemistry major at Rice, I was required to take molecular biophysics. I saved that for the very last semester because I was fairly certain I was going to flunk this course, and I didn’t want the ‘F’ to be on my graduate school transcript. But I had already decided, ‘I’m going to suffer through this terrible course that has been prescribed to me.’”
And then: eureka. “From the very first day, I loved it. I remember the exact day, even the chair I was sitting in, in the lecture hall, when the professor explained to me that by using X-rays, and the scattering of the X-rays, one could mathematically calculate a topographical map of the location of every electron in a protein, and how much it moved from that position. And you could see a thing which was sub-microscopic. It was like the clouds parting, and light came out. That was what I wanted to do with the rest of my life, because it was the most intellectually exciting thing I had ever heard, that if you could write down the set of mathematical equations, the set of molecular structure of something, and how it’s folded, and how if this mine of information got knit into a three-dimensional moving structure of a machine, you could write down and calculate anything you would need to know about the function of that molecule. It should be written in that structure. That was what I was going to do: I was going to reveal these structures. So we did!”
She holds up a blue and yellow model of a tiny virus. “This is a piece of the inner workings of a Lassa virus, and this, in the center, in purple, orange and green, is the surface protein. This is the molecule it uses to attach to a human cell and drive it in. What we’re showing you here are antibodies, and each one [that] has a hole in it is a different antibody, [which we collected] from a human survivor from villages in Sierra Leone and Nigeria. You’re looking at and holding how these humans have survived this virus.”
I don’t fully understand what I’m looking at, but I do know that it is remarkable, and that this remarkable woman’s love affair with some of the greatest killers on the planet may save us all from becoming future statistics.
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