As we build up to the 3rd SCI-RSC symposium on antimicrobial drug discovery, we spoke to Dr Anita Shukla, Associate Professor of Engineering at Brown University, about designing drug delivery systems to treat infection, creating a positive atmosphere in her lab, the challenges facing professionals in her industry, and much more.
Anita Shukla, Associate Professor of Engineering at Brown University
Tell us a bit more about the work being done in your lab.
All of what my lab works on is very biomedically orientated. The major thing we focus on is treating bacterial and fungal infections. We have a lot of interest in designing drug delivery systems to treat all sorts of bacterial and fungal infections, from localised infections to more systemic infections. We design nanoparticles, polymeric nanoparticles, self-assembled structures, surface coatings and larger-scale materials such as hydrogels that can be used as bandages.
We work on the material design for delivering antimicrobial therapeutics – antibiotics, antifungals and other antimicrobial components – and we study a lot about the properties of these materials. What sets us apart is that we’re trying to make materials that are smart, that are in some way targeted or responsive to the presence of bacteria or fungi.
So, to give you an example, we are working on making hydrogel wound dressings. These wound dressings are smart and can respond to the presence of bacteria and fungus. They know when bacteria and fungi are present, based on the enzymes that are there in the localised local environment of the hydrogel. They actually degrade only in the presence of those enzymes and release encapsulated nanotherapeutics.
And that’s really important because of antimicrobial resistance. So, we are trying very hard to provide effective therapies but limit exposure to antimicrobial therapeutics only to times that they’re needed. That’s the kind of work we’ve been doing over the past five or six years.
You’ve done some really interesting work on pregnancy care too. Tell us more about that.
So, that work was inspired by a graduate student who was very interested in women’s health and prenatal health. What we noted was that a lot of pharmaceutical agents that you must use when you’re pregnant don’t have enough information associated with their potential toxic side effects on a growing fetus. A lot of that testing is very difficult to do, so we thought: ‘Can we come up with model systems that could be used for the testing of pharmaceutical agents, toxins, and toxicants?’
The placenta really is the interface between the fetus and the mother and a lot of the nutrient and waste exchange happens through this organ. We wanted to come up with a model system that represents a placenta that was cell free and didn’t involve using an animal. So, what we did was we first studied cells taken from a placenta and the lipid composition of these cells, and then we made lipid bilayers out of synthetic lipids that mimicked the composition of placental cells at different trimesters during the pregnancy. And then we looked at how different small molecules (some of them were actually antimicrobial therapeutics) interact with these synthetic lipid bilayer models.
We noted the differences between the different trimesters and compositions of the placental cells in terms of the lipid content and how these toxicants, small molecules and pharmaceutical agents interacted. It’s early stage work but that same technology could be adapted for the purpose of high throughput testing in a cell-free environment for a range of applications.
What you do in your lab has a real-world effect. How important is that?
We’re very real-world application driven. I think the science is great, and we do a lot of fundamental science in the lab too, but the purpose is to solve real-world problems. Right now, with the pandemic, the work we’re doing on antimicrobial drug delivery is very relevant. The data show that bacteria and fungal co-infections for patients that have Covid-19 are increasing greatly and that’s heavily problematic. The antimicrobial resistance issue is just going to be exacerbated because these patients can also receive antibiotics and antifungals at the same time.
Finding solutions to real-life problems at the Shukla Lab. Image courtesy of Brown University School of Engineering
How did you get to this point in your career?
The one big factor in where I ended up is my family. My family has always supported me tremendously and I’ve had a very positive role model of an academic and researcher in my father. That definitely got me early exposure, which exemplifies and solidifies the fact that early exposure is really important, which can come from your family, friends, teachers, and other role models.
When I started my undergraduate studies at Carnegie Mellon University, I thought I wanted to go into medicine at first, but then when I got there. I really enjoyed designing solutions that physicians would use. As an undergrad, I didn’t really know what I wanted to do in terms of the exact field of research; so, every summer I did a different research experience. In the first summer, I worked at the University of Rhode Island in a Mechanical Engineering lab. For the second summer, I worked at MIT in a materials science lab. And for my third summer, I worked in Columbia University in applied physics and mathematics. I also did research at Carnegie Mellon University with a faculty member in chemical engineering and just tried to get mentors and different experiences under my belt so I could get better informed in what I wanted to do. I then went to MIT to study chemical engineering for my graduate degrees.
Did any specific people help you along the way?
I worked with a faculty member at MIT, Paula Hammond, who’s now the department Head in Chemical Engineering at MIT. She was really an amazing influence for me. I definitely had strong female role models as an undergrad, but my graduate supervisor at MIT happened to be a strong black female scientist and that was hugely influential to me – to see that you can be a minority in STEM, really successful, and do it all. At the same time, she was very open about challenges for women in chemical engineering and not afraid to talk about it at all. She did a great job in promoting us and making sure we had the right mentoring during the five years of my PhD. So, I’m very grateful to her.
I did my postdoc at Rice University in the bioengineering department, and I worked with another really strong female mentor there. My postdoctoral advisor, Jennifer West – who is now the Dean of Engineering at the University of Virginia – was really amazing. I learnt a whole new set of things from her. In all of this, I can pinpoint that I’ve had many mentors. I would highly advise that regardless of what you are interested in doing in life, find those people who are out there to support you.
How did you end up at Brown?
I ended up at Brown in the School of Engineering as a tenure track assistant professor in the summer of 2013. Since then, all the time has gone into setting up my lab and advancing our science. It’s pretty much flown by. I’ve been extremely lucky. I’ve had amazing students and postdocs in my lab. They really produce everything that comes out of it. I’m just the spokesperson.
I love working with them. We have a very inclusive environment. We talk about a lot of diversity, equity, and inclusion-related concerns. I think that’s really important. We try to self-educate and educate each other on these topics. We have a welcoming environment and genuinely care that everyone in the lab feels respected. Because you can only do good science and good work if you work in a place where you are happy and respected and can be yourself.
What does a given working day look like?
It varies. A given day is chaotic due to work and having two small kids. My husband is also a professor at Brown so we both have similar demands on our time but a lot of my time goes into research and proposal writing. We need to raise funds to run a lab so we definitely spend a lot of time on that. Paper writing to get out work out is also super important.
My favourite things are meeting with my grad students and postdocs about research. I love meeting with them and talking with them about their data and generating new ideas together. This semester I am also teaching a class about advances in biomedical engineering over the past couple of years. Preparing those classes and making sure I am devoting time to them is important to me.
‘One thing I always tell students is don’t doubt yourself. Go ahead and try.’ Image courtesy of Brown University School of Engineering
What challenges have you had to overcome in your career?
I've been extremely lucky, but there has been the two-body situation. It’s essentially having a working spouse and trying to figure out how to make it work so that you both have the careers you want in the same location. That took me and my husband five years to figure out.
My husband was in Texas and I was in Rhode Island and I had two babies with me while doing this academic career on my own. That’s incredibly challenging, but it’s extremely common. In general, I think industry and academia need to work harder to make it easier for individuals to figure out this situation and smoothen the transition.
There are other little things that come up that are challenging. I do often feel that I have to prove myself to my older male colleagues at times when I shouldn't have to. If I get into an elevator with a male colleague who’s exactly the same age as me, a senior male colleague might ask that colleague about his research, and I might be asked about my kids. I often think it’s not intentional – and I try to give people the benefit of the doubt – but I think there’s a lot of education that still needs to be done.
>> Interested in the latest on antimicrobial drug discovery? Register to attend the 3rd SCI-RSC symposium on antimicrobial drug discovery on 15 and 16 November.
What’s the current state of play in your sector with respect to diversity, equality, and inclusion?
There's a lot to do but there’s a lot more awareness now. We’re far from where we need to be in terms of representation of all sorts of individuals in academia. Really, it’s ridiculously appalling if we look at numbers of black individuals, women in STEM academics, or the grant funding that goes to these individuals. But I have seen over the past two years or so that there’s just been more people talking about it. In biomedical engineering, a group of around 100 faculty or so academics around the US gets together periodically over Zoom to talk about these topics, and there’s more awareness and content in our scientific forums.
What’s the greatest challenge for people developing antimicrobial materials or in biomedical areas?
With therapeutics, it’s the FDA approval timeline. It’s years later by the time they’re used. A lot of the time people shy away from working in therapeutics because they know how hard it is going to be to commercialise something in that area.
On an academic level for me as an engineer, it’s critical to figure out what the important challenges and problems are. We’re very lucky at Brown that we have a great medical school so we can talk to clinicians, but cross-talk between disciplines is super important right now.
What advice would you give to young professionals in your area?
One thing I always tell students is don’t doubt yourself. Go ahead and try. You can’t win a game if you don’t play it. I constantly run into individuals who say: ‘I didn’t apply for that because I didn’t think I was qualified’. Basically, I just tell them to apply – you have nothing to lose.
What are you and your students working on that you’re most excited about at the moment?
I really love everything we are doing! I love the fact that we are designing materials that are smart, so they respond to the presence of microbes. I think that could be groundbreaking in terms of prolonging the lifetime of our existing antimicrobial drugs. We also have some really great work going on in treating biofilms, which are incredibly problematic in terms of infections. It’s very hard to answer. I’m proud of everything we do.