Siva Sankari

About me

I work at the interface of biochemistry, microbial physiology, plant biology, and bioengineering to study host-microbe interactions.
Host Peptides play an important role in governing the molecular combat between host and microbes. They are studied for their anti-microbial, anti-cancer and immune-modulatory functions. In my recent study , I have shown that host peptides are also capable of directly modulating the cellular metabolism of symbiotic bacteria for the benefit of the host and have the potential to be translated to a variety of clinical applications outside symbiosis.
My lab will study the mechanism of action of host peptides to understand host-microbe interactions and translate them to clinical and agricultural applications to improve human health and sustainability.

I am currently looking for tenure track faculty positions for Fall 2023. Please contact me if your institution is hiring! Click here for my CV

As a Postdoctoral Research Scientist in Dr. Graham Walker’s lab at MIT, apart from discovering a major novel insight into the molecular mechanisms underlying host-microbe interactions, I have also developed robust tools to study the mechanistic details of any anti-microbial/symbiotic peptides that act on bacteria. In my doctoral study in Dr. Mark O’ Brian's Lab, at the University at Buffalo, I discovered and analyzed important mechanisms of iron import, trafficking, and export in the bacterium Bradyrhizobium japonicum with agriculturally important leguminous host plant-Soybean. During my Master’s in Biotechnology, I worked on building metabolic networks to optimize the production of PHA by Pseudomonas putida and Reuterin by Lactobacillus reuteri.

Research interests

Peptide biology

Peptides in legumes-soil bacteria interactions have existed for more than ~50 Mya. More than 700 “Nodule-specific Cysteine-Rich” (NCR) peptides are produced by the host plant Medicago truncatula and have evolved to orchestrate the terminal differentiation process of symbiotic bacteria and enslave them to fix nitrogen for the plant. Since they belong to defensin-like family, the anti-microbial activity of a few NCR peptides is being explored for clinical applications. However, only recently have we known that these peptides have evolved to fine-tune the cellular metabolism of bacteria through multiple pathways when used at sublethal, physiologically relevant concentrations. In fact, my work was the first to clearly demonstrate this idea through detailed mechanistic studies of one of the NCR peptides. The knowledge of how exactly these peptides act on bacteria will shed light on important aspects of host-microbe interactions in other systems. My work also demonstrated that studying the biochemistry of these peptides can help us develop clinical applications beyond the anti-microbial arena of NCR peptides. I am interested in studying their detailed mechanism of action and exploiting them in developing various clinical applications both within and outside of the bacterial context.

Therapeutic Applications

Additionally, I will continue to explore and extend the various avenues of therapeutic applications of extremely tight heme binding by plant peptide NCR247 that I started during my post-doc.

Sustainable Agriculture

Chemical pesticides are detrimental to the environment and human health. I will work on improving sustainability in agriculture by developing plant products as alternatives to chemical pesticides and by improving biological N2 fixation as an alternative to chemical fertilizers.

Iron homeostasis

Iron is an essential nutrient for both microbes and their host. I am fascinated by the nuances of microbial iron homeostasis, how this essential, yet toxic, resource is delicately shared between the host and symbiotic bacteria. I am interested in studying the role of host peptides in maintaining this balance.

Selected Publications

Discovery of heme binding to NCR247- Mechanistic studies and development of potential therapeutic applications

Using a variety of biochemical, bioanalytical, microbiological, and plant genetic techniques, we have unraveled the first detailed molecular mechanism of a heme-binding, symbiotically essential plant peptide NCR247 that takes control of bacterial iron homeostasis and tricks the symbiotic bacterium into importing excess iron needed for nitrogen-fixation. Leveraging the unique heme-binding properties of the peptide, we have developed many potential therapeutic applications including inhibiting the growth of some heme-requiring pathogens and parasites, preventing the formation of fungal biofilms, preventing the toxic peroxidase activity of Aβ-heme complex associated with Alzheimer’s disease, and removing toxic free heme accumulated in stored blood.
Sankari, S., Babu, V.M.P., Bian, K. et al. Nat Microbiol (2022).
Full Text viewable
The fun and adventurous "Behind the Paper" story of how this project unraveled
MIT News : "Scientists identify a plant molecule that sops up heme"
Other News articles: Phys.org; The Science advisory board; Faculty Opinions

How do bacteria import iron into the nodules?

I showed that FeoAB system is required for ferric and ferrous iron utilization in free-living Bradyrhizobium japonicum. More importantly, FeoAB is required for the transport of iron into bacteroids during symbiosis and is essential for a successful symbiosis with Soybean. This is the first study to identify the mechanism of iron transport into bacteria during symbiosis.
S. Sankari and M.R. O'Brian, J Biol Chem, 291(30): p. 15653-62, 2016.

Need for iron detoxification for normal bacterial functioning

Here I found that iron export and iron storage work in concert. Through various genetic experiments, I have demonstrated that iron detoxification is not limited to extreme environments but to normal functioning of the bacteria.
S. Sankari and M.R. O'Brian, PLoS One, 11(6): p. e0157250, 2016.

Do bacteria export iron? Why and How?

Nutritional iron import was well studied, yet almost nothing was known about iron export. This is the first study to demonstrate iron export in bacteria. By using many genetic and biochemical analyses I showed that MbfA is an inner membrane protein involved in iron export. More importantly, I showed that iron export plays a very important role in the maintenance of iron homeostasis in bacteria.
S. Sankari and M.R. O'Brian. J Biol Chem, 289(23): p. 16498-507, 2014.

For full list of publications, click here

Teaching, Diversity and Outreach

Teaching experience

1) Curriculum developer and Co-Instructor- MIT Course 6. A01. A combined classroom and laboratory course for MIT undergraduates as part of Tiny Earth Initiative, Oct-Dec 2019.

2) Kaufman Teaching Certificate Program and Microteaching training at MIT, June 2019.

3) Teaching assistant- BCH403/503 –Course on Biochemical principles for Undergraduate and Master students in Department of Biochemistry, University at Buffalo (Fall 2012)

4) Lecturer (June 2009 –April 2010) - Sri Venkateshwara College of Engineering, Sriperumbudur, India. Course instructor for undergraduate courses-Protein Engineering and Advanced Genetic Engineering. Course instructor for laboratory courses- Recombinant DNA technology, Molecular biology

Student testimonials can be found at Linkedin

Commitment to Diversity and Outreach

Being a first-gen woman hailing from a small town, I had to break many social and economic barriers to pursue higher studies and choose a career in research. I noticed that students like myself hailing from rural places lacked exposure to hands-on research, knowledge on the opportunities available and guidance on the steps that needed to be taken to pursue research as a career. This lays on top of all the social and economic barriers the students have to face. I have noticed that this has led many hard-working, smart women to deter from science and as scientists, I feel it is our responsibility to provide an equal and inclusive environment for everyone who wish to do science.

Following are some of the steps I have taken so far towards lessening the knowledge gap on research opportunities and providing much-needed mentorship to students (especially girls) hailing from rural and underprivileged communities.

ReAct Program

I am a member of the founding team and Coordinator of ReAct - a mentorship program for undergraduate students with limited exposure to research. This program aims at developing scientific temperament and improving the accessibility of STEM education to undergraduates. I am very proud to announce that our first cohort of mentor–mentee group has started in June 2022 and is currently undergoing training. ReAct is organized by Sci-ROI –a program of WinStep forward.

Kalpana Program

I am a curriculum developer and member of the instructor team in Kalpana SHE for STEM Incubator

Kalpana is a career development and mentoring program which successfully places every girl on a high confidence STEM path. She-For-STEM program gives female STEM undergraduates access to expert mentoring by relatable-role models and provides tools for continuous self-development, advanced research projects and career plans.

I was a mentor in the MIT Summer Research program (MSRP) and trained 2 students in summer of 2018 and 2022.

Editorial Activities

I am an Assistant Features Editor at Molecular Plant-Microbe Interactions (APS) journal. If you are a graduate student-first author on any recent or upcoming article in MPMI and would like to tell your story behind the paper, please contact me. If you are a corresponding author and want to highlight the excellent work of your graduate and undergraduate students towards the publication, please contact me. I also serve as a guest editor at JoVE.

Career guidance activities

I have also given Career guidance talks to students from various parts of India and undergraduates to encourage them to take up scientific research as a career and to introduce them to nuances of developing scientific temperament.