Visualizing cellular building blocks using high-resolution cryo-EM
What We Do
the idea
We want to visualize how proteins within our cells organize information at the atomic level.
the methods:
1. high-resolution cryo-EM
We focus on using single-particle cryo-EM to visualize protein structure at near-atomic resolution. Taking biochemically purified protein, we ‘flash-freeze’ or vitrify our sample in liquid ethane. Imaging this in Cornell’s Arctica/K3 electron microscope, we are able to achieve sufficiently high resolution (< 3Å on ‘ideal’ systems) to trace the atomic structure of the protein we are studying. We have used this technique to obtain multiple structures between 3-4 Å resolution, which isn’t high enough resolution to directly see each atom’s position, however with computational modeling of protein structure, we can infer the placement of these atoms very accurately!
2. computational modeling
Modeling can provide useful insight when used to interpret cryo-EM maps, especially for maps > 3.5 Å resolution. In our pioneering study describing tau’s physiological structure (previously thought to be intrinsically disordered), use of sophisticated structure modeling tools (Rosetta) was required to infer the most energetically favorable structure of tau. Branching off of this idea, we will work to develop methodologies that will utilize Rosetta to infer the architecture of complexes ranging from near-atomic to low-resolution cryo-EM data.
the idea
We want to visualize how proteins within our cells organize information at the atomic level.
the methods:
1. high-resolution cryo-EM
We focus on using single-particle cryo-EM to visualize protein structure at near-atomic resolution. Taking biochemically purified protein, we ‘flash-freeze’ or vitrify our sample in liquid ethane. Imaging this in Cornell’s Arctica/K3 electron microscope, we are able to achieve sufficiently high resolution (< 3Å on ‘ideal’ systems) to trace the atomic structure of the protein we are studying. We have used this technique to obtain multiple structures between 3-4 Å resolution, which isn’t high enough resolution to directly see each atom’s position, however with computational modeling of protein structure, we can infer the placement of these atoms very accurately!
2. computational modeling
Modeling can provide useful insight when used to interpret cryo-EM maps, especially for maps > 3.5 Å resolution. In our pioneering study describing tau’s physiological structure (previously thought to be intrinsically disordered), use of sophisticated structure modeling tools (Rosetta) was required to infer the most energetically favorable structure of tau. Branching off of this idea, we will work to develop methodologies that will utilize Rosetta to infer the architecture of complexes ranging from near-atomic to low-resolution cryo-EM data.
Why join the Kellogg lab?
A close-knit team
In small labs that are just starting up (like the Kellogg lab), you will get an intimate look at how labs are run and what it is like to start a lab. Teamwork is crucial at this stage, and we emphasize this in our own lab.. Everyone is expected to help one another! As with many other small and growing labs, Liz is most often found in the lab at her bench helping with experiments or providing hands-on training for her lab members.
Obtain unique training in exciting and growing fields
Computational modeling with Rosetta
The Kellogg lab has the unique combination of backgrounds. Rosetta is a powerful software suite that is capable of accurate protein structure prediction and sophisticated protein design. We routinely use Rosetta to aid us in interpreting the results of our structural studies, and we have ideas for Rosetta-based design projects that would help with cryo-EM structure determination.
High-resolution cryo-EM
It is an incredible time to be doing cryo-EM. The field is fast-paced, exciting, and growing. In the Kellogg lab we recognize the full power of cryo-EM to study not just structure but dynamics. We want to combine both of these powerful techniques to study how protein conformation and function are linked in protein complexes that are refractory to other structural techniques (crystallography, NMR, etc). As the only lab at Cornell trained and specialized in biological high-resolution cryo-EM, you can expect training from the best!
Work creatively across disciplines
We are an interdisciplinary lab: Molecular and Cellular Biology, Chemistry, Physics, and Computer Science are all topics of interest in the Kellogg lab’s research program. An interdisciplinary training is extremely powerful as a scientific foundation and an area of focus for funding agencies and institutions. Don’t worry if you aren’t an expert in all of these topics, we’re all here to learn and that’s what teamwork is for!
Strength in diversity and culture
We emphasize respect for all cultures and backgrounds. We value each individual, and we respect and acknowledge their personal experiences. In the Kellogg lab, we value diversity, in identity as well as discipline.
A big community
We are part of two large communities: the Rosetta community and the cryo-EM community.
The Rosetta community is a tight-knit community that spans the globe. As a member of the Kellogg lab, you will have access to developers and other learning opportunities offered to those in this community. We regularly attend RosettaCon and interact/collaborate with Rosetta community members.
As part of the cryo-EM community, you can expect to participate in local and national CryoEM meetings.
In small labs that are just starting up (like the Kellogg lab), you will get an intimate look at how labs are run and what it is like to start a lab. Teamwork is crucial at this stage, and we emphasize this in our own lab.. Everyone is expected to help one another! As with many other small and growing labs, Liz is most often found in the lab at her bench helping with experiments or providing hands-on training for her lab members.
Obtain unique training in exciting and growing fields
Computational modeling with Rosetta
The Kellogg lab has the unique combination of backgrounds. Rosetta is a powerful software suite that is capable of accurate protein structure prediction and sophisticated protein design. We routinely use Rosetta to aid us in interpreting the results of our structural studies, and we have ideas for Rosetta-based design projects that would help with cryo-EM structure determination.
High-resolution cryo-EM
It is an incredible time to be doing cryo-EM. The field is fast-paced, exciting, and growing. In the Kellogg lab we recognize the full power of cryo-EM to study not just structure but dynamics. We want to combine both of these powerful techniques to study how protein conformation and function are linked in protein complexes that are refractory to other structural techniques (crystallography, NMR, etc). As the only lab at Cornell trained and specialized in biological high-resolution cryo-EM, you can expect training from the best!
Work creatively across disciplines
We are an interdisciplinary lab: Molecular and Cellular Biology, Chemistry, Physics, and Computer Science are all topics of interest in the Kellogg lab’s research program. An interdisciplinary training is extremely powerful as a scientific foundation and an area of focus for funding agencies and institutions. Don’t worry if you aren’t an expert in all of these topics, we’re all here to learn and that’s what teamwork is for!
Strength in diversity and culture
We emphasize respect for all cultures and backgrounds. We value each individual, and we respect and acknowledge their personal experiences. In the Kellogg lab, we value diversity, in identity as well as discipline.
A big community
We are part of two large communities: the Rosetta community and the cryo-EM community.
The Rosetta community is a tight-knit community that spans the globe. As a member of the Kellogg lab, you will have access to developers and other learning opportunities offered to those in this community. We regularly attend RosettaCon and interact/collaborate with Rosetta community members.
As part of the cryo-EM community, you can expect to participate in local and national CryoEM meetings.