Tuli Lab

The Tuli Lab was born in 2005 in Bloomington, Indiana.

Our lab is focused on examining molecular interactions required for efficient assembly and release of infectious virus particles. For a virus to be infectious it is important the pieces go together in the right order and at the right time.

We work with alphaviruses which are enveloped, positive-strand RNA viruses that are transmitted to a variety of vertebrate hosts primarily by mosquitoes. Alphavirus virions are icosahedral and consist of the viral genome, 240 copies of the capsid and spike proteins, and a host-derived lipid bilayer.

Our lab is interested in identifying how the genome, proteins, and lipids assemble together to form an infectious particle. We use a combination of genetic, biochemical, cell biological, and structural approaches to study virus assembly.

Check out our research section to see what we are pursuing these days. Keep up with lab happenings by following @TuliLab .

Our Research

These are the main research interests of our lab. We are also involved in many collaborations, see our publications section to read about those endeavors.

Spike Assembly

The viral spikes on the surface of the virus particle are absolutely required for cell entry. Misassembled spikes can mean a less infectious virus. In addition, the spikes interact directly with the internal core suggesting a role in particle stability. How do these trimeric spikes form?

Some questions we are asking:

  • What are the different conformations of the glycoproteins during spike assembly?
  • When and where do the spikes interact with the capsid proteins?
  • What is the function(s) of E3 during assembly?
  • What do 6K and TF do during spike assembly?

Check out what our lab has found about spike assembly

Nucleocapsid core

The core must balance between protecting the viral genome during transmission and then at then in response to the proper trigger releasing the genome to initiate an infection.

Some questions we are asking:

Viral budding and spread

Alphaviruses are transmitted by arthropods to a wide range of vertebrate hosts. In both cases the virus buds from the plasma membrane as it spreads through the animal.

Questions we’re asking:

Nanoparticles

Core assembly can be recapitulated in vitro using purified protein and different "cargo" or encapsidated molecules. The goal of this work is to create virus-like particles which are virus particles that contain different cargo. The cargo can be molecules of medical imaging, drug delivery, or gene therapy.

Some questions we are asking:

  • What types of cargo can be incorporated into core particles?
  • How can we efficiently make virus-like particles that target specific cells?

Check out these papers from our lab related to this work

People

Tuli, the PI

PhD, University of Illinois, Chicago, advisor Wonhwa Cho

First postdoc UTSW, advisor Elliott Ross

Second postdoc Purdue University, advisor Michael Rossmann

Google Scholar Page

Alan Moore

Biochemistry graduate student

Jolene Ramsey

Microbiology graduate student

LinkedIn

Julie Button

Biochemistry graduate student

I am graduate student in the Biochemistry program at IU. I completed my undergraduate education in 2014 at West Virginia University with B.S. degrees in Chemistry and Forensic Science with a concentration in Chemistry. I also completed minors in Biology and Business Administration. I then took a year off where I completed two Science Undergraduate Laboratory Internships (SULI) through the Department of Energy (DOE) at Lawrence Livermore National Laboratory, as well as completing part of a post-baccalaureate position at the lab before leaving to start graduate school. I joined the Tuli lab in 2016. After completing my PhD, my goal is to become a research scientist at a government laboratory, such as the NIH, USDA, or one of the national laboratories.

See Julie's CV

Sara Jones-Burrage

Postdoc

I have a B.A. from Agnes Scott College in Molecular Genetics and Biochemistry. I completed my Ph.D. at Baylor College of Medicine with Dr. James Versalovic. During my thesis studies, I examined factors secreted from biofilms that mediate probiotic activities of Lactobacillus reuteri. My first postdoc was in Dr. Katherine Knight’s laboratory at Loyola University Medical Center; during my postdoc, I identified molecules and pathways involved in anti-inflammatory commensal:host interactions.

Sunna Ahmad

Undergraduate student

I am a junior at Indiana University, hoping to pursue a career in dentistry. I am a Microbiology major, also obtaining a Spanish minor. I am involved with the IU Research Undergraduate Journal (IUJUR), Pre-Dental Society, and STARS here at IU, and enjoy reading and baking in my free time.

Nicholas Adams

Undergraduate student

Makanvi Talawali

Undergraduate student

I am a senior majoring in Biology with concentration in Cell Biology and Genetics and minoring in Chemistry. I hope to attend graduate school and earn a degree in Molecular and Cellular Biology or Bioengineering.

Lab Alumni

  • Megan Parrott Dunn, Lecturer, Department of Biology, Indiana University
  • Fan Cheng, postdoc Gao lab, University Southern California
  • AJ Snyder, postdoc Danthi Lab, Indiana University
  • Christina Melki, Assistant Professor, Corbin University
  • Holly Thornton, Eli Lilly, Indianapolis
  • Jennifer Balke, Nursing school
  • Brian Towell, SureTech Laboratories
  • Bella Chavez, Medical Interpreter, Goshen Health System
  • Kevin Sokoloski, Assistant Professor, University of Louisville
  • Vamsee Rayaprolu, postdoc Kohout lab, Montana State University
  • Zhenning Tan, Henlix, Inc
  • Kaila Schollaert, Clinical Research Coordinator, University of Pittsburgh
  • Chelsea Hayes, Research Associate, Indiana University
  • Many wonderful undergraduates….

    Rohit Devnani, Mark Forster, Sarah Sitarski, Jeff Stutler, Asha Jamzadeh, Jonathan Pike, Nicole Richey, Kyle Glass, Phil Forys, Adam Leibold, Lana Khuong, Jessica Gonzalez, Peju Oshodi, Madeline Ehrlich

Lab publications

Spike Assembly

  • Parrott, M. M., Sitarski, S. A., Arnold, R. J., Picton, L. K., Hill, R. B., and Mukhopadhyay, S. (2009) Role of Conserved Cysteines in the Alphavirus E3 Protein. J. Virol. 83(6): 2480-2490.
  • Snyder, A. J., Sokoloski, K. J., and Mukhopadhyay, S. (2012) Mutating conserved cysteines in the alphavirus E2 glycoprotein causes virus-specific assembly defects. J. Virol. 86(6):3100-11.
  • Snyder, A. J. and Mukhopadhyay, S. (2012) The Alphavirus E3 protein functions in a clade-specific manner. J Virol. 86(24):13609-20.
  • Zeng, X., Mukhopadhyay, S., Brooks III, C. L. (2015) Residue level resolution of alphavirus envelope protein interactions in pH dependent fusion. PNAS. 112(7):2034-9.

Nucleocapsid core

  • Cheng, F. and Mukhopadhyay, S. (2011) Generating enveloped virus-like particle with in vitro assembled cores. Virology. 413(2):153-60.
  • Sokoloski, K.J., Snyder, A.J., Liu, N.H., Hayes, C.A., Mukhopadhyay, S., and Hardy, R.W. (2013) Encapsidation of host-derived factors correlates with enhanced infectivity of Sindbis virus. J. Virol. 87(22):12216-12226.
  • Sokoloski, K.J., Haist, K.C., Morrison, T.E., Mukhopadhyay, S. and Hardy, R.W. (2015) NonCapped Sindbis virus genomic RNAs and their role during Alphaviral infection. J. Virol. 89(11):6080-92.
  • Chao, C., Wang, C-Y., Rayaprolu, V., Mukhopadhyay, S., and Zlotnick, A. (2015) Self-assembly of an Alphavirus core-like particle is distinguished by strong intersubunit association energy and structural defects. ACS Nano. 9(9):8898-8906.

Viral budding and spread

  • Sokoloski, K.J., Hayes, C.A., Dunn, M.P., Balke, J.L., Hardy, R.W., and Mukhopadhyay, S. (2012) Sindbis virus infectivity improves during the course of infection in both mammalian and mosquito cells. Virus Res. 167(1):26-33.
  • Tsvetkova, I.B., Cheng, F., Ma, X., Moore, A.W., Howard, B., Mukhopadhyay, S., and Dragnea, B. (2013) Fusion of mApple and Venus fluorescent proteins to the Sindbis virus E2 protein leads to different cell-binding properties. Virus Res. 177(2):138-146.
  • Tsetsarkin, K.A., Chen, R., Yun, R., Rossi, S.L., Plante, K.S., Guerbois, M., Forrester, N., Perng, G.C., Sreekumar, E., Leal, G., Huang, J., Mukhopadhyay, S., and Weaver, S.C. (2014) Multi-peaked Aedes albopictus-adaptive landscape for chikungunya virus evolution predicts continued increases in transmissibility. Nat Commun. 16(5):4084-4097.
  • Ramsey, J., Renzi, E.C., Arnold, R.J., Trinidad, J.C., Mukhopadhyay, S. (2016) Palmitoylation of Sindbis virus TF protein regulates its plasma membrane localization and subsequent incorporation into virions. J. Virol. 91(3). pii: e02000-16.

Nanoparticles

  • Goicochea, N.L., De, M., Rotello, V.M., Mukhopadhyay, S., and Dragnea, B. (2007) Core-like particles of an enveloped animal virus can self-assemble efficiently on artificial templates. NanoLetters. 7(8):2281-90.
  • Cheng, F., Tsvetkova, I.B., Khuong, Y., Moore, A.W., Arnold, R.J., Goicochea, N.L., Dragnea, B., and Mukhopadhyay, S. (2013) The packaging of different cargo into enveloped viral nanoparticles. Molecular Pharmaceutics. 10(1):51-8.

Other cool science

  • Zlotnick, A.* and Mukhopadhyay, S.* (2011) Virus assembly, allostery, and antivirals. Trends in Microbiology. 19(1):14-23.
  • Lai, Y., Yi, G., Chen, A., Bhardwaj, K., Valverde, R.A., Zlotnick, A., Mukhopadhyay, S., Ranjith-Kumar, C.T., and Kao, C.C. (2011) Viral double-strand RNA-binding proteins can enhance innate immune signaling by Toll-like receptor 3. PlosOne. 6(10):e25837.
  • Snyder, A.J., Mukherjee, S., Glass, J.K., Kearns, D.B., and Mukhopadhyay, S. (2014). The canonical twin-arginine translocase components are not required for secretion of folded GFP from B. subtilis. J. Applied and Environmental Microbiology, 80(10):3219-3232.
  • Li, Z., Dilger, J. M., Pejaver, V., Smiley, D., Arnold, R.J., Mooney, S., Mukhopadhyay, S., Radivojac, P., and Clemmer, D. (2014) Intrinsic Size Parameters for Palmitoylated and Carboxyamidomethylated Peptides. Inter. J. Mass Spec. 368:6-14.
  • Mohari, B., Licata, N.A., Kysela, D.T., Merritt, P.M., Mukhopadhyay, S., Brun, Y.V., Setayeshgar, S., and Fuqua, C. (2015) Novel pseudotaxis mechanisms improve migration of straight swimming bacterial mutants through a porous environment. mBio. 6(2) e00005-15.
  • Khanal, N., Pejaver, V., Li, A., Radivojac, P., Clemmer, D.E., and Mukhopadhyay, S. (2015) The position of proline mediates the reactivity of S-palmitoylation. ACS Chem. Biol. 10(11):2529-2536.
  • Myagmarjav, B.E., Konkol, M.A., Ramsey, J., Mukhopadhyay, S., Kearns, D.B. (2016) ZpdN, a plasmid-encoded sigma factor homolog, induces pBS32-dependent cell death in Bacillus subtilis. J Bacteriol. 198:2975–2984.

Funding

We thank all our former and current funding sources supporting research and people:

  • National Science Foundation
  • NIH: National Institute of Allergy & Infectious Disease
  • MetaCyte
  • Assembly Biosciences
  • NIH training grants T32 GM109825 and T32 GM007757, the American Society for Microbiology, and Indiana University (Floyd, Taylor, Konetzka, Mower, Putnam, and Lilly Biocomplexity) for funding predoctoral fellowships

Contact

Department of Biology
Indiana University
Simon Hall MSBI, Room 220C
212 S. Hawthorne Drive | Bloomington, IN 47405-7003
Phone: 812-856-3686 | sumukhop@indiana.edu

Lab
Shipping Address:
Mukhopadhyay Lab
1001 E. Third Street
Bloomington, IN 47405
Phone: (812) 856-3633
Fax: (812) 856-5710

We are always looking for enthusiastic, smart, creative people to join the lab.

Graduate students: Please apply to the Microbiology PhD program through the Department of Biology or the Biochemistry PhD program through the Department of Molecular and Cellular Biochemistry.

Postdocs: Please email Tuli directly at sumukhop@indiana.edu and attach a CV.

Undergraduates: Please email Tuli directly at sumukhop@indiana.edu.