Tell us about your research
My research looks at how biological systems process metals. Metals are co-factors for 40% of proteins. Apart from humans, there is bacteria, viruses and many other organisms that use metals for enzymatic process or capsid proteins. I am specifically looking at the host-pathogen interface. Bacteria keep looking at sources of metal such as Iron, Manganese, Calcium, etc. Also, there are metals that human body uses that bacterium don’t, especially copper. The bacteria at the host-pathogen interface that ends up infecting humans use very low amounts of copper, thus copper in even low concentrations can be detrimental. This brings the focus on how the body uses Copper to kill the bacteria. Also, humans have been taking advantage of the bactericidal property of Copper. For example, in Bordeaux mixture in vineyards and to eradicate potato blight disease. Our body also uses nutritional immunity, where bacteria are restricted from getting the metals they like (Iron, Manganese, etc.) and bombard them with copper. This mechanism is seen in macrophages. My laboratory focuses on three major questions surrounding Copper:
- Using Streptococcus pneumoniae as the primary bacterial model we study the toxicity of copper,
- the bacterial defense mechanism against copper toxicity, and
- Weaponizing Copper as a therapeutic.
We know that Copper causes mis-metalation and destabilizes the protein by disrupting the active site. At the same time, bacteria have copper exporters that acts as defense mechanism. Finally, we now can use Copper as a weapon by utilizing a Copper chelator or Ionophore that binds with copper and increases the amount of copper inside the cell by 60-fold! Going a bit deeper on the second aspect, we have discovered the relationship between sugar uptake and the redox reaction of Cu2+ to Cu1, where the latter leaves the bacterial cell. In other words, the sugar acts as an electron source for reducing Cu2+ to Cu1, and there is an upregulation of the gene responsible for sugar uptake. Where is the sugar coming from? Since, the capsule of S. pneumoniae is made of sugar, it became clear that the bacteria use the nearest source of sugar as electron source. In a way, cannibalizing its own protective capsule for exporting copper out of its system
What were your challenges of being a NewPI and how you overcame them?
As a new PI, the biggest challenge was figuring out which expectations took priority at a given point of time: The institution’s priorities or the department’s or myself. The reason is that in the first year of a NewPI, there are lots of sucker punches that come along the way, in terms of everything going as per plan. In these situations, my expectations then have to change with the times I was dealing with. And, that by itself was a challenge. With changing expectations and fulfilling my own, there had to be a comfort in the chaotic nature of what those changes look like. How to deal with changes and still feel confident in the realistic expectations, becomes the key to look at things. Coming from a high (I am going to save the world, 10 times over!) to the realistic expectations of all encompassing of what other people need from you and what you want from yourself. This was the biggest challenge for me.
In order to overcome these, I work with my expectations and I ask myself “Did I address a research question to the best of my ability?” “Did I make a fundamental contribution in research/mentoring/outreach/teaching?” and what level of satisfaction I get in this position. Basically, a refocus of priorities inside-out.
How have you been coping with the pandemic in terms of mentoring and research?
The pandemic led me to create something that is far more valuable than my research in the laboratory. I saw that many were missing on research opportunities, and I decided to do something about it. I made the National Summer Undergraduate Research Project that connect mentors to mentees, virtually. COVID-19 made this program possible in 11 days! In the first year we had 250 students in two different cohorts, and 170 mentors world-wide participate. These students got an opportunity if not for this program. In the next year, we go NSF RAPID award for providing a full-time stipend to 66 students matched to 63 mentors! And this program is now a three-year REU for microbiology and immunology that got funded by the NSF. We are looking at areas to expand and incorporate other disciplines such as cancer biology. One of the important questions asked to the students was if they are interested to travel for an in-person program, if COVID goes away. A third of them said no and others said they were unsure, as they had family of their own, financial obligations, caring for parents, etc. So, this program is meeting the people where they are at, rather than the other way around and find a seat at the table. Our program will always stay virtual to provide the opportunities for those who want to get research experience. Outreach is more transformative part of my research and I channelized COVID challenges into this successful, transformative, and a positive program.
As a NewPI, what’s your superpower?
The ability to connect people and connecting ideas are my superpowers!
In this academic rollercoaster ride, words of motivation for others?
Celebrate everything! We want to wait until the finish line before we celebrate. But there are many things to celebrate to give a peace of mind. So, every small thing is a moment for celebration and we need to reward ourselves to motivate ourselves. The people around me, my lab members need to see me celebrate like that, because small victories, medium victories, large victories are all victories. Don’t wait for big events! You earned it! The #humblebrag channel is the best, it is best antidote for a bad mood. It makes you feel better seeing other people’s victories and successes. We can get it together.
What is the one piece of advice you would give to your past self, on the day 1 of this job?
Go for the equipment you need to get the job done. Don’t wait! No buyer’s remorse. There is a story from childhood when I was in the little league that I never forget. I didn’t get one single hit in my first two years of baseball. I was either ducked or struck out. It was the playoffs and I was crouching as small as possible and I thought the ball that came was way outside and didn’t swing. The umpire called “Strike three!” and I was dejected since I thought it was outside! But, as I was walking away, the umpire said “You gotta swing the bat, Son”. It was good life lesson for me.
What’s the coolest factoid about copper and bacteria that I never knew I needed to hear/know?
The coolest thing about copper is that it exists in the interface between our body and bacteria. Copper intoxication happens very quickly with microbes! There is certain level of elegance in living in that crevice. It is a pretty looking metal. There is this wonderful unknown that exists about near and dear things we use everyday and keep exploring those environments/platforms related to copper.