Gas-filled Protein Nanostructures

Protein Engineering | Cell Therapies | Living Materials | Ultrasound

Gas vesicles are a group of genetically encoded protein nanostructures that can assemble inside cells and create nanoscale stable air compartments. We leverage their unique acoustic, optical, and magnetic properties and develop creative solutions to address challenges from biomedicine to material science.

 

We are recruiting!

Ph.D. Students:

We are looking for talented and passionate graduate students who are interested in a variety of projects on protein engineering, synthetic biology, cell therapies, ultrasound imaging, biomanufacturing, and living materials. Prospective students are encouraged to reach out to Dr. Lu (george.lu at rice.edu) with their CV and a statement of interest to discuss the opportunities in the lab. Rice offers several outstanding Ph.D. programs relevant to our research: (1) Bioengineering program that are ranked among the top 10 in the coutry, (2) Systems, Synthetic, and Physical Biology (SSPB), an elite graduate program aiming focusing on engineering biological systems, and (3)  Applied Physics program, which offers a unique multidisciplinary research experience.

Master Students:

Prospective master students are encouraged to apply to Rice’s Master of Bioengineering program. Please note that we recently added a Research-Based track in addition to the previous Class-Based track under the Applied Bioengineering concentration. While both tracks provide opportunities for one to conduct research projects in an individual lab, the research track provides more resources and time. See here for details.

Undergraduate Students:

We are looking for motivated undergraduate students who are interested in doing research. Please feel free to email your inquiries to Dr. Lu (george.lu at rice.edu).

Postdoctoral Fellows:

We are actively seeking talented and motivated postdoctoral fellows to join our multidisciplinary group. Candidates with experience and interest in the following fields are particularly encouraged to apply: ultrasound imaging physics, living materials, synthetic biology, and microbial engineering. Please see any one of the following job advertisements: Ultrasound Imaging Physicist, general, and the search for the most updated Rice University post.

Research Assistants:

We are looking for motivated research assistants who are interested in conducting resarch projects. Please feel free to email your inquiries to Dr. Lu (george.lu at rice.edu).

 

What We Do

Image and control cell therapies

Ultrasound can noninvasively reach the targets at centimeter-deep tissue. We develop protein sensors and genetic circuits that render cells visible and controllable by ultrasound.

Protein assembly engineering

A group of 8-12 proteins works cooperatively to form the gas-filled protein nanostructures. We aim to understand and design the structure, function, and assembly of these unique protein nanostructures.

Living materials

Engineered living materials (ELMs) are living cells that autonomously form the material and can often modulate the functional performance and sense the surrounding environments. We leverage the optical, mechanical, and acoustic properties of gas vesicles to create ELMs with unique material properties.

Engineer biology in the mesoscopic domain

The mesoscopic domain is defined to be between the size of a single protein and that of a cell. Our long-term vision is to engineer biology in this domain to provide innovative solutions to world.

Who We Are

George J. Lu

George J. Lu

PI, SynMA Group
Assistant Professor of Bioengineering
george.lu@rice.edu

Xingzheng Sun (Jason)

Xingzheng Sun (Jason)

Ph.D. Student, Bioengineering
B.Sc., UC Los Angeles
xingz@rice.edu

Yuqing Han

Yuqing Han

Ph.D. Student, Bioengineering
B.Sc. Tsinghua U
yuqing.han@rice.edu

Diana Barr

Diana Barr

Ph.D. Student, Bioengineering
B.Sc., U Mass Amherst
db107@rice.edu

Andy Liu

Andy Liu

Undergraduate researcher,
B.Sc., Rice University, expected 2027
al168@rice.edu

Zongru Li

Zongru Li

Ph.D. Student, Bioengineering
M.Sc., Northwestern U
B.Sc., U of Rochester
zongru.li@rice.edu

Chia-Yu Ho (Johnny)

Chia-Yu Ho (Johnny)

PhD student, Bioengineering
M.Sc. & B.Sc., National Tsing Hua University
chia-yu.ho@rice.edu

Eman Fayyaz

Eman Fayyaz

Undergraduate researcher,
B.Sc., Rice University, expected 2027
eman.fayyaz@rice.edu

Kathy Xiao Cai

Kathy Xiao Cai

Ph.D. Student, Bioengineering
B.Sc., Texas A&M University
kx11@rice.edu

Manuel Iburg

Manuel Iburg

DFG Postdoctoral Fellow
Ph.D. Humboldt University
M.Sc. & B.Sc., Leibniz U of Hanover
manuel.iburg@rice.edu

Rishab Mandyam

Rishab Mandyam

Undergraduate researcher,
B.Sc., Rice University, expected 2027
rishab.mandyam@rice.edu

Paul Kim

Paul Kim

Ph.D. Student, Bioengineering
B.Sc., Rice University
pk27@rice.edu

Mohamed Mohamed

Mohamed Mohamed

Ph.D. Student, Bioengineering
M.Sc., Carnegie Mellon U

B.Sc., Syracuse U
mm272@rice.edu

Eugene Chung

Eugene Chung

Ph.D. Student, Bioengineering
B.Sc. Arizona State U
epc2@rice.edu

Chungwon Kang

Chungwon Kang

Ph.D. Student, Bioengineering
M.Sc. & B.Sc., Dongguk University, Korea
chungwon.kang@rice.edu

Jaiden Vera

Jaiden Vera

High-school researcher,
DeBakey High School, expected 2025

Angela Cai

Angela Cai

Undergraduate researcher,
B.Sc., Rice University, expected 2026
aqc3@rice.edu

Sumin Jeong

Sumin Jeong

Undergraduate researcher,
B.Sc., Rice University,
expected 2025
sj71@rice.edu

Jiayang Liu (Gary)

Jiayang Liu (Gary)

Postdoctoral Fellow,
Ph.D. Jiangnan University
gl61@rice.edu

Somesh Skanda

Somesh Skanda

MBE student in Applied Bioengineering
B.Sc., Loyola College
somesh.skanda@rice.edu

Sanjay Senthilvelan

Sanjay Senthilvelan

Undergraduate researcher,
B.Sc., Rice University, expected 2027
ss352@rice.edu

Photos and Fun

Summer group photo 2021

 

 

 

 

 

 

 

 

Beach party 2021

 

 

 

 

 

 

 

 

Lab dinner 2021

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Birthday parties

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

News

Our preprint manuscript Elucidating the assembly of gas vesicles by systematic protein-protein interaction analysis is now on bioRxiv. Big cheers to Manuel Iburg and all other co-authors from the lab. Please also see the Twitter and LinkedIn posts.

July, 2023

Our preprint manuscript Spatial Organization of Gas Vesicles is Governed by Phase-separable GvpU is now on bioRxiv. Congratulations to Zongru Li and Nicole Shen for leading this project as well as other co-authors from the lab. Please also see the Twitter and LinkedIn posts.

May, 2023

Congratulations to Eugene Chung for receiving the prestigious NSF Graduate Research Fellowship Program (GRFP).

April, 2023

Congratulations to our undergraduate student, Vivian Wong, for receiving the Distinction in Research and Creative Works award at her graduation.

April, 2023

Congratulations to Manuel Iburg for receiving the prestigious German Research Foundation (DFG) postdoctoral fellowship.

July, 2022

We received support from the Heating Health Foundation for our collaboration with the Raphael Group to develop molecular imaging agents for monitoring Ménière’s disease. See news.

October, 2021

Congratulations to our undergrad student Ramiro Cantu for winning the Summer Undergraduate Research Fellowships (SURF).

April, 2021

Our preprint manuscript 50-nm gas-filled protein nanostructures to enable the access of lymphatic cells by ultrasound technologies is now on bioRxiv. Congratulations to Nicole Shen and Zongru Li for leading this project as well as other co-authors from the lab. Please also see the Twitter and LinkedIn posts.

June, 2023

Congratulations to Jimmy Dickantone for winning the Summer Undergraduate Research Fellowship (SURF) and the Award for Excellence in Poster Presentations at Rice Summer Undergraduate Research Symposium.

August, 2022

We received support from John S. Dunn Foundation for developing treatments for pancreatic cancer. See the Rice news.

September, 2022

The preprint manuscript Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET presents the high-resolution structure of gas vesicles and is now on bioRxiv.

July, 2022

Congratulations to our gradudate student Zongru Li for winning the 2022 IBB Student Travel Award.

March, 2022

Congratulations to our postdoc Manuel Iburg for being selected as a Junior Fellow in the Rice Academy of Fellows.

September, 2021

We received funding support from the Mathers Foundation to develop gas vesicles as the acoustic reporter genes. See news.

April, 2021

We received funding support from the Welch Foundation to study gas-filled protein nanostructures. See news.

April, 2021

 

Miscellaneous

Open Positions

Outreach

Publications

Donation

Teaching

Contact

 

Publications

Spatial organization of organelles

Spatial organization of organelles

bioRxiv, 2023.06.01.543273

Microbes pack gas vesicles into tight bundles to save their cytosolic space, and yet the molecular mechanism underlying this process remains unknown. Here we discovered the protein governing this process and the intriguing phase separation behavior of this protein.

Virus-size ultrasmall bubbles

Virus-size ultrasmall bubbles

bioRxiv, 2023.06.27.546433

Here we have shrunk gas vesicles (GVs) to the size of a virus, and to our knowledge, these are the smallest stable, free-floating bubbles made to date. Check out these 50-nm GVs and our demonstration of their ability to penetrate into deep tissues in lymph nodes.

GV assembly roadmap

GV assembly roadmap

bioRxiv, 2023.07.23.550228

Gas vesicles (GVs) are microbial gas-filled protein organelles that have been repurposed recently for a diverse set of biomedical applications such as ultrasound imaging of gene expression and ultrasound-mediated delivery. GVs do not self-assemble inside bacteria and instead require a coordinated effort of ~10 proteins to assemble. As a first step to unravel this intriguing cellular process, we constructed a systematic protein-protein interaction map, which led to hypotheses of protein clusters for each stage of the assembly. We anticipate the work will lay the foundation to solve the molecular mechanism of GV assembly.

Journal Articles

  1. Iburg M, Anderson AP, Wong VT, Anton ED, He A, Lu GJ (2023) Elucidating the assembly of gas vesicles by systematic protein-protein interaction analysis. bioRxiv, 2023.07.23.550228 Tweet, LinkedIn.
  2. Shen Q, Li Z, Meyer MD, De Guzman MT, Lim JC, Bouchard RR, Lu GJ (2023) 50-nm gas-filled protein nanostructures to enable the access of lymphatic cells by ultrasound technologies. bioRxiv, 2023.06.27.546433 Tweet, LinkedIn.
  3. Li Z, Shen Q, Dai Y, Anderson AP, Iburg M, Lin R, Zimmer B, Meyer MD, You L, Chilkoti A, Lu GJ (2023). Spatial organization of gas vesicles is governed by phase-separable GvpU. bioRxiv, 2023.06.01.543273 Tweet, LinkedIn.
  4. Dutka P, Metskas LA, Hurt RC, Salahshoor H, Wang TY, Malounda D, Lu GJ, Chou TF, Shapiro MG, Jensen GJ (2023). Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET. Structure, 31, 518-528 e516
  5. Dutka P, Malounda D, Metskas LA, Chen S, Hurt RC, Lu GJ, Jensen GJ, Shapiro MG (2021) Measuring gas vesicle dimensions by electron microscopy. Protein Science 30, 1081-1086.
  6. Lu GJ, Chou L, Malounda D, Patel AK, Welsbie DS, Chou DL, Ramalingam T, Shapiro MG (2020) Biomolecular contrast agents for optical coherence tomography. ACS Nano 14, 7823–7831.
  7. Kunth M, Lu GJ, Witte C, Shapiro MG, Schröder L (2018) Protein nanostructures produce self-adjusting hyperpolarized magnetic resonance imaging contrast through physical gas partitioning. ACS Nano 12, 10939-10948.
  8. Lu GJ #, Farhadi A#, Mukherjee A, Shapiro MG (2018) Proteins, air and water: reporter genes for ultrasound and magnetic resonance imaging. Current Opinion in Chemical Biology 45, 57-63. (# co-authors)
  9. Maresca D, Lakshmanan A, Abedi M, Bar-Zion A, Farhadi A, Lu GJ, Szablowski JO, Wu D, Yoo S, Shapiro MG (2018) Biomolecular Ultrasound and Sonogenetics. Annu. Rev. Chem. Biomol. Eng. 9, 229-252.
  10. Lu GJ, Farhadi A, Szablowski JO, Lee-Gosselin A, Barnes SR, Lakshmanan A, Bourdeau RW, Shapiro MG (2018) Acoustically modulated magnetic resonance imaging of gas-filled protein nanostructures. Nature Materials 17, 456-463. News & Views  |  Featured on the journal cover  |  Media news  | Behind the paper
  11. Farhadi A, Ho G, Kunth M, Ling B, Lakshmanan A, Lu GJ, Bourdeau RW, Schröder L, Shapiro MG (2018) Recombinantly Expressed Gas Vesicles as Nanoscale Contrast Agents for Ultrasound and Hyperpolarized MRI. AIChE Journal 64:2927–2933.
  12. Lakshmanan A #, Lu GJ #, Farhadi A #, Nety SP #, Kunth M, Lee-Gosselin A, Maresca D, Bourdeau RW, Yin M, Yan J, Witte C, Malounda D, Foster FS, Schröder L, Shapiro MG (2017) Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI. Nature Protocols 12(10):2050-2080. (# co-authors)
  13. Mukherjee A, Davis HC, Ramesh P, Lu GJ, Shapiro MG (2017) Biomolecular MRI reporters: Evolution of new mechanisms. Prog. Nucl. Magn. Reson. Spectrosc. 102-103:32-42.
  14. Maley AM, Lu GJ, Shapiro MG, Corn RM (2017) Characterizing Single Polymeric and Protein Nanoparticles with Surface Plasmon Resonance Imaging Measurements. ACS Nano 11(7):7447-7456.
  15. Barskiy DA, Coffey AM, Nikolaou P, Mikhaylov DM, Goodson BM, Branca RT, Lu GJ, Shapiro MG, Telkki V-V, Zhivonitko VV, Koptyug IV, Salnikov OG, Kovtunov KV, Bukhtiyarov VI, Rosen MS, Barlow MJ, Safavi S, Hall IP, Schröder L, Chekmenev EY (2017) NMR Hyperpolarization Techniques of Gases. Chemistry 23(4):725-751.
  16. Radoicic J, Lu GJ, Opella SJ (2014) NMR structures of membrane proteins in phospholipid bilayers. Q. Rev. Biophys. 47(3):249-283.
  17. Tian Y, Lu GJ, Marassi FM, Opella SJ (2014) Structure of the membrane protein MerF, a bacterial mercury transporter, improved by the inclusion of chemical shift anisotropy constraints. J. Biomol. NMR 60(1):67-71.
  18. Lu GJ, Opella SJ (2014) Resonance assignments of a membrane protein in phospholipid bilayers by combining multiple strategies of oriented sample solid-state NMR. J. Biomol. NMR 58(1):69-81.
  19. Lu GJ, Opella SJ (2014) Mechanism of dilute-spin-exchange in solid-state NMR. J. Chem. Phys. 140(12):124201.
  20. Lu GJ, Opella SJ (2013) Motion-adapted pulse sequences for oriented sample (OS) solid-state NMR of biopolymers. J. Chem. Phys. 139(8):084203.
  21. Lu GJ, Tian Y, Vora N, Marassi FM, Opella SJ (2013) The structure of the mercury transporter MerF in phospholipid bilayers: a large conformational rearrangement results from N-terminal truncation. J. Am. Chem. Soc. 135(25):9299-9302.
  22. Das BB, Nothnagel HJ, Lu GJ, Son WS, Tian Y, Marassi FM, Opella SJ (2012) Structure determination of a membrane protein in proteoliposomes. J. Am. Chem. Soc. 134(4):2047-2056.
  23. Lu GJ, Park SH, Opella SJ (2012) Improved 1H amide resonance line narrowing in oriented sample solid-state NMR of membrane proteins in phospholipid bilayers. J. Magn. Reson. 220:54-61.
  24. Son WS, Park SH, Nothnagel HJ, Lu GJ, Wang Y, Zhang H, Cook GA, Howell SC, Opella SJ (2012) ‘q-Titration’ of long-chain and short-chain lipids differentiates between structured and mobile residues of membrane proteins studied in bicelles by solution NMR spectroscopy. J. Magn. Reson. 214(0):111-118.
  25. Lu GJ, Son WS, Opella SJ (2011) A general assignment method for oriented sample (OS) solid-state NMR of proteins based on the correlation of resonances through heteronuclear dipolar couplings in samples aligned parallel and perpendicular to the magnetic field. J. Magn. Reson. 209(2):195-206.
  26. Marassi FM, Das BB, Lu GJ, Nothnagel HJ, Park SH, Son WS, Tian Y, Opella SJ (2011) Structure determination of membrane proteins in five easy pieces. Methods 55(4):363-369.
  27. Knox RW, Lu GJ, Opella SJ, Nevzorov AA (2010) A Resonance Assignment Method for Oriented-Sample Solid-State NMR of Proteins. J. Am. Chem. Soc. 132(24):8255-8257.
  28. Cherney LT, Cherney MM, Garen CR, Lu GJ, James MNG (2008) Crystal Structure of the Arginine Repressor Protein in Complex with the DNA Operator from Mycobacterium tuberculosis. J. Mol. Biol. 384(5):1330-1340.
  29. Cherney LT, Cherney MM, Garen CR, Lu GJ, James MNG (2008) Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr 64(Pt 9):950-956.
  30. Lu GJ, Garen CR, Cherney MM, Cherney LT, Lee C, James MNG (2007) Expression, purification and preliminary X-ray analysis of the C-terminal domain of an arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 11):936-939.

Patent

  1. Lu GJ, Shapiro MG, Farhadi A, Szablowski JO. Gas-filled structures and related compositions, methods and systems for magnetic resonance imaging. Filed July 28, 2017, Application Number: US 15/663,600.

Cover Art

Gas-filled MRI contrast agents

Gas vesicles derived from photosynthetic microbes are shown to elicit magnetic resonance imaging contrast in vitro and in vivo with the potential for acoustically modulated multiplexing and molecular sensing.

Image by Barth van Rossum. Cover Design by David Shand.

 

Teaching

BIOE 505 Macromolecular Assemblies

Synopsis: There is increasing attention on the biological phenomena and engineering opportunities at the mesoscopic scale, which is between the size of a single protein and that of the large organelles. This course will cover a range of these phenomena, such as viral particles, ribosomes, bacterial microcompartments, amyloid fibrils, gas vesicles, and membraneless condensates. Additionally, the course will aim to formulate physical principles behind these phenomena, describe the experimental and computational approaches to study them, and discuss how to engineer these assemblies.

 

Donation

Your donation will help advance our research and education towards cell-based therapies for cancer and new biodegradable materials.

Online donations:

Visit the School of Engineering Donation Page
Enter gift amount
From the Designation pull-down menu choose “Other”.
In the Special Instructions box type “Lu Lab Donation”

Mail in donations:

Send your check to the address below and earmark it specifically for the Lu Lab
Rice University
Office of Development MS-81
P.O. Box 1892
Houston, TX 77251-1892

If you need further information, please email giving@rice.edu or call 713-348-4991. Please also feel free to directly contact Dr. George Lu (george.lu@rice.edu).

 

Contact

Lab location: BioScience Research Collaborative (BRC)

Address: 6500 Main St., BRC 670, Houston, TX 77030

Email: x@rice.edu and replace x with george.lu

Links: Campus Map; BRC building

 

Our Funding