IGP:
Life Sciences

Mentor / Lab:
Dr. Nicholas Noinaj

Specific Research Area / Project:
Structural and Functional Studies of Lactoferrin Binding Proteins from Neisseria

Undergraduate Institution:
Indian Institute of Technology Roorkee, India

Research Profile:

Neisseria are exclusive human pathogens causing meningitis, septicemia, bacteremia and gonorrhea diseases. During pathogenesis, Neisseria bacterium employs TonB-dependent surface receptors to obtain iron from iron-containing host glycoproteins including transferrin, lactoferrin, and hemoglobin. The lactoferrin binding protein (Lbp) system hijacks lactoferrin and has been hypothesized to hijack iron from it for its own survival and also actively employs measures to evade the host immunity. The Lbp system is composed of two components: lactoferrin binding protein A (LbpA), an outer membrane protein, and lactoferrin binding protein B (LbpB), an extracellular surface anchored lipoprotein. Additionally, LbpB provides protection against host and synthetic cationic antimicrobial peptides. However, the molecular mechanisms of the Lbp system’s functions are unknown due to the absence of structural and biochemical studies. Therefore, this knowledge gap has hindered the development of Lbp-based protein-conjugate vaccines and antibiotics.

The overall goal of our research is to investigate the iron import and antimicrobial peptide protection functions of the Lbp system. To accomplish our goals, we utilize structural biology techniques such as X-ray crystallography, cryo-electron microscopy, small-angle X-ray scattering etc, which will assist in our structure-guided mutagenesis and thermodynamic binding studies. Our research will provide structural basis of the Lbp system’s role in Neisserial pathogenesis and pave the way for understanding the molecular mechanism of these functions. The gained knowledge will be utilized for structure-based drug/vaccine discovery and development.

About Me:

I joined PULSe program in August 2016 and have enjoyed every single day at Purdue University. To me, the most interesting aspect of PULSe program was to rotate in different labs prior to joining a permanent lab. Taking full advantage of this opportunity, I rotated in labs working on various aspects of biological science research covering virology, cell culture, bacterial pathogenesis, X-ray crystallography and cryo-electron microscopy. Eventually, I joined Dr. Nicholas Noinaj’s lab where we utilize a multi-disciplinary approach to study outer membrane proteins of Gram-negative bacteria. Along with excellent research environment, PULSe program also provides a platform to interact with kids and motivate them to pursue a career in research. I volunteered at various events like Science in School (SiS) and Spring Fest. One of my favorite memories from these events was to create lava lamps at Spring Fest which excited the kids and parents alike. I am looking forward to my next few years at Purdue University and am excited about what new experiments I may get to perform at the SiS events.

Awards:

• Certificate of Excellence in Interdisciplinary Research (Life Sciences), OIGP spring reception, Purdue University, USA (2018)
• Lynn Fellowship, Purdue University, USA (2016)

Publications:

• Megha Aggarwal, Ramanjit Kaur, Amrita Saha, Rajat Mudgal, Ravi Yadav, Paban Kumar Dash, Manmohan Parida, Pravindra Kumar, Shailly Tomar (2017). Evaluation of antiviral activity of piperazine against Chikungunya virus targeting hydrophobic pocket of alphavirus capsid protein. Antiviral Research, 146: 102-111.
• Shivendra Pratap*, Aditya Dev*, Vijay Sharma*, Ravi Yadav*, Manju Narwal, Shailly Tomar, Pravindra Kumar (2017). Structure of chorismate mutase-like domain of DAHPS from Bacillus subtilis complexed with novel inhibitor reveals conformational plasticity of active site. Scientific Reports, 7 (1):6364. (* represents co-first authors).
• Shivendra Pratap, Pooja Kesari, Ravi Yadav, Aditya Dev, Manju Narwal, Pravindra Kumar (2017). Acyl chain preference and inhibitor identification of Moraxella catarrhalis LpxA: Insight through crystal structure and computational studies. International Journal of Biological Macromolecules, 96: 759-765.

Presentations:

• Ravi Yadav, Srinivas Govindan, Tommi White, Srinivas Chakravarthy, Jia Ma, Nicholas Noinaj (2018). Structural insight into Neisseria meningitidis lactoferrin binding protein B’s interaction with human lactoferrin. Hitchhiker’s Guide to Biomolecular Galaxy Symposium, Purdue University, West Lafayette, IN, USA.
• Ravi Yadav, Srinivas Govindan, Tommi White, Srinivas Chakravarthy, Jia Ma, Nicholas Noinaj (2018). Structural characterization of Lactoferrin binding protein B – Lactoferrin complex. 13th Midwest Conference on Protein Folding, Assemblies and Molecular Motions, University of Notre Dame, IN, USA.
• Ravi Yadav, Srinivas Govindan, Tommi White, Srinivas Chakravarthy, Jia Ma, Nicholas Noinaj (2018). Structural characterization of Lactoferrin binding protein B – Lactoferrin complex. OIGP Spring Reception, Purdue University, West Lafayette, IN, USA. (Certificate of Excellence in Interdisciplinary Research)
• Ravi Yadav, Nicholas Noinaj (2018). Targeting antibiotic resistance in pathogenic bacteria: Structure and Function of Membrane Proteins. Biological Sciences Interview Weekend, Purdue University, West Lafayette, IN, USA.
• Ravi Yadav, Srinivas Govindan, Tommi White, Srinivas Chakravarthy, Nicholas Noinaj (2017). Structural characterization of Lactoferrin binding protein B – Lactoferrin complex. Department of Biological Sciences Fall 2017 Retreat, Purdue University, West Lafayette, IN, USA.
• Ravi Yadav, Thu Cao, Andrew Miller, Richard J Kuhn (2017). Insight into NS1 protein’s role in Flavivirus infection. Purdue University Interdisciplinary Life Science (PULSe) Spring Reception, West Lafayette, IN, USA.
• Ravi Yadav, Madhusudhan K. Rao, Pooja Kesari, Neha Singh, Vijay Sharma, Anamika Singh, Pravindra Kumar (2016). Structure based drug design towards new anti-infective drugs. 1st Annual Biotechnology Day Poster Session, IIT Roorkee, India (3rd prize).
• Structural insight into Neisseria meningitidis lactoferrin binding protein B’s interaction with human lactoferrin. (2018) Hitchhiker’s Guide to Biomolecular Galaxy Symposium, Purdue University, West Lafayette, IN, USA.
• Structural insight into Neisseria meningitidis lactoferrin binding protein B’s interaction with human lactoferrin. (2018) 13th Midwest Conference on Protein Folding, Assemblies and Molecular Motions, University of Notre Dame, IN, USA.

Leadership:

• Volunteer at Science in School (SiS) events organized by PULSe program (2016 - 2017)
• Volunteer at Spring Fest events organized by PULSe program (2017)
• Judge for Sigma Xi Senior Life Sciences (LS) Special Award category at 65th Annual Lafayette Regional Science and Engineering Fair 2017
• Judge for Biochemistry category at 66th Annual Lafayette Regional Science and Engineering Fair 2018