Nsf-ari-grant

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:* Individual research descriptions go here
:* Individual research descriptions go here
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Research (K. J. Seu)
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The structure and dynamics of membrane proteins is one of the most important and challenging problems in biophysical chemistry today. Dr. Kalani Seu is interested in protein-lipid interactions and the changes that occur in both the lipid bilayer and the protein as the two interact. In Seu’s research, isotope-edited FTIR is used to obtain residue specific structural and hydration information of peptides as they interact with synthetic lipid vesicles and supported lipid bilayers(1,2). Complementary techniques including ATR-FTIR, fluorescence spectroscopy, circular dichroism, and fluorescence microscopy are also used. Use of these techniques provides detailed insight into the mechanism of protein folding, insertion, hydration, and function in the presence of a lipid membrane. This information will improve our understanding of how proteins interact with and act on biological membranes, providing insights for the design and development of tools for disease treatment and drug development. 
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Some key questions of Seu’s research include: How are the lipids near the protein oriented to accommodate the presence of the protein and what kind of environment surrounds each of the protein residues? Are the residues hydrated, non-hydrated, or partially hydrated? Do the structural and hydration states change as the lipid composition is altered? Can isotope-edited FTIR be used to identify bilayer spanning regions of larger proteins?
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Recent work by Seu has been focused on a 21-residue peptide, KL4, which has been successfully used in clinical trials to replace lung surfactant protein B. Using isotope-edited FTIR, residue specific differences were observed in the secondary structure of KL4 at different positions in the peptide backbone when incorporated into lipid vesicles of varying saturation(3). These results are in agreement with those obtained by SS-NMR4(5).  Unlike SS-NMR, isotope-edited FTIR is a faster and more efficient technique that can provide the medium-resolution information necessary to map out peptide structure and hydration.
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From mid-June to mid-July 2009, Seu and two students used the biochemistry research area to identify changes in the structure and solvation state of model helical peptides incorporated into lipid bilayers.  These model peptides are similar in sequence to that of KL4 and have been thoroughly studied in solution.  Changes in the FTIR amide I? band of these peptides in buffer, lipids, and fluorinated solvents were monitored for changes in secondary structure and shifts due to solvation state.  Slight differences in peak position, peak shape, and melting curves were observed, suggesting changes in solvation state and structural stability.
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(1) Decatur, S. M. Accounts of Chemical Research 2006, 39, 169.
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(2) Tamm, L. K.; Tatulian, S. A. Quarterly Reviews of Biophysics 1997, 30, 365.
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(3) Seu, K. J.; Long, J. R.; Decatur, S. M. Biophysical Journal 2009, 96, 336a.
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(4) Antharam, V. C.; Elliott, D. W.; Mills, F. D.; Farver, R. S.; Sternin, E.; Long, J. R. Biophysical Journal 2009, 96, 4085.
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(5) Mills, F. D.; Antharam, V. C.; Ganesh, O. K.; Elliott, D. W.; McNeill, S. A.; Long, J. R. Biochemistry 2008, 47, 8292.
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--[[User:Seuka|Seuka]] 19:53, 23 July 2009 (UTC)

Revision as of 19:53, 23 July 2009

Major Questions to address

1. Why are the spaces we are renovating one facility?
- one building (in fact only one end of the building)
- all spaces are for shared use (not dedicated to a single faculty user) and are organized by function
- research facility helps serve the research training needs of our shared major


2. What collaborations do we envision in our facility? How will these future collaborations improve the research at Earlham?
- past collaborations - Keck, HHMI, Merck-AAS


3. Why do we need to renovate? What do we envision doing in the new space that we cannot do now?
- building limitations (water, house air, vacuum, electrical,...)
- spaces inadequate for shared use of modern instruments and significant increase in # of instruments
- need spaces intentionally designed to facilitate collaborations (open design)
- spaces inadequate for multi-faculty, multi-project use
- increased # of faculty, students doing research needs all of the above


4. What distinguishes us from other institutions?
- history of multidisciplinary work (perhaps highlight Keck work)
- emphasis on ensuring research exposure for large number of students
- the numbers (grad school, % of majors in college,......)


Research statements Identify the senior personnel using the research facility for research/research training. Describe their research activities--identifying the specific questions being addressed, projects conducted in the facility, and sources of support, if any. In narrative or tabular form, list by number and type (e.g., senior personnel, postdoctoral fellows, graduate students, undergraduate students) the personnel using the facility on a regular basis.


  • Individual research descriptions go here

Research (K. J. Seu)

The structure and dynamics of membrane proteins is one of the most important and challenging problems in biophysical chemistry today. Dr. Kalani Seu is interested in protein-lipid interactions and the changes that occur in both the lipid bilayer and the protein as the two interact. In Seu’s research, isotope-edited FTIR is used to obtain residue specific structural and hydration information of peptides as they interact with synthetic lipid vesicles and supported lipid bilayers(1,2). Complementary techniques including ATR-FTIR, fluorescence spectroscopy, circular dichroism, and fluorescence microscopy are also used. Use of these techniques provides detailed insight into the mechanism of protein folding, insertion, hydration, and function in the presence of a lipid membrane. This information will improve our understanding of how proteins interact with and act on biological membranes, providing insights for the design and development of tools for disease treatment and drug development.

Some key questions of Seu’s research include: How are the lipids near the protein oriented to accommodate the presence of the protein and what kind of environment surrounds each of the protein residues? Are the residues hydrated, non-hydrated, or partially hydrated? Do the structural and hydration states change as the lipid composition is altered? Can isotope-edited FTIR be used to identify bilayer spanning regions of larger proteins?

Recent work by Seu has been focused on a 21-residue peptide, KL4, which has been successfully used in clinical trials to replace lung surfactant protein B. Using isotope-edited FTIR, residue specific differences were observed in the secondary structure of KL4 at different positions in the peptide backbone when incorporated into lipid vesicles of varying saturation(3). These results are in agreement with those obtained by SS-NMR4(5). Unlike SS-NMR, isotope-edited FTIR is a faster and more efficient technique that can provide the medium-resolution information necessary to map out peptide structure and hydration.

From mid-June to mid-July 2009, Seu and two students used the biochemistry research area to identify changes in the structure and solvation state of model helical peptides incorporated into lipid bilayers. These model peptides are similar in sequence to that of KL4 and have been thoroughly studied in solution. Changes in the FTIR amide I? band of these peptides in buffer, lipids, and fluorinated solvents were monitored for changes in secondary structure and shifts due to solvation state. Slight differences in peak position, peak shape, and melting curves were observed, suggesting changes in solvation state and structural stability.

(1) Decatur, S. M. Accounts of Chemical Research 2006, 39, 169. (2) Tamm, L. K.; Tatulian, S. A. Quarterly Reviews of Biophysics 1997, 30, 365. (3) Seu, K. J.; Long, J. R.; Decatur, S. M. Biophysical Journal 2009, 96, 336a. (4) Antharam, V. C.; Elliott, D. W.; Mills, F. D.; Farver, R. S.; Sternin, E.; Long, J. R. Biophysical Journal 2009, 96, 4085. (5) Mills, F. D.; Antharam, V. C.; Ganesh, O. K.; Elliott, D. W.; McNeill, S. A.; Long, J. R. Biochemistry 2008, 47, 8292. --Seuka 19:53, 23 July 2009 (UTC)


  • ideas for collaborative research go here



Identify as a single research structure with 5 shared research areas, each with a specific function (rather than dedicated for a single researcher). Describe each area (current and proposed).


1. Identify and describe the research facility including its nature, location, size, configuration, purpose, age, condition, and date of major repair, refurbishment and/or last renovation, if any.


- use description of SH as whole
- need details of past renovations of each area to do this
- renovations under Lilly grant in this area (move in hoods only?)
- other renovations - minor changes to adapt space when psychology went to LBC


2. Discuss the adequacy, limitations, and constraints of the facility and the relevant impact of these conditions on research/research training activities in that facility.


- limitations of the building (water, air, nitrogen, electric, benches,…)


- limitations that are in common
- small spaces – limit use by multiple users
- inadequate configuration (benches, hoods)


- special limitations – describe any that are specific to discipline
- molecular
- biochem
- analysis
- synthesis


3. Indicate what research and research training that is not now feasible in the facility would be enabled by the proposed infrastructure project.


- examples for whole building work


- examples for each area



4. Identify the specific space to be upgraded, the square footage of the facility, and indicate the percentage of time that the facility is used for research and research training and the fraction of space used for these purposes. Include the rationale for percentage determination if either is less than 100%.


- describe whole facility or describe each area


5. The description of needs should be comprehensive enough to allow reviewers to evaluate the extent to which the facility improvement is essential and appropriate.

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