Protein Research and Being Human in STEM: Professor Jaswal wins 2021 Carl Branden Award


The Protein Society presents the Carl Brändén Award to an outstanding protein scientist who demonstrates dedication to service and education. Professor Sheila Jaswal received this year’s award for pioneering Being Human in STEM (HSTEM) at Amherst in addition to her research on protein structure and dynamics. I had a lovely discussion with Dr. J about (1) her research, (2) the story behind HSTEM, and (3) how students can get involved in HSTEM now.


Research


Dr. Jaswal’s lab performs research in protein folding. Proteins are large molecules that perform important functions in our bodies including catalyzing reactions, regulation, and transmitting biological signals. Proteins are synthesized in our bodies in three distinct steps: transcription of a DNA sequence to an mRNA sequence, translation of the mRNA sequence to an amino acid chain, and folding of the protein into its final functional structure. To understand protein folding, Dr. J focuses specifically on monitoring folded proteins, which are actually constantly unfolding and folding back up, continuously going through the different stages of protein folding from the floppy unfolded amino acid chain to the fully functional structure, in a process known as protein dynamics.


“The focus of our research is understanding the folding, stability and dynamics of proteins under native (physiological) conditions.” Essentially, how is the protein flopping around into and out of its functional structure, and how do those protein dynamics determine the protein’s role in normal biology and in disease? “While we understand how we go from the DNA sequence to the amino acid sequence, what we don't understand so well is how that amino acid sequence dictates the final three dimensional structure that the protein folds up into. Over the last couple of years, there have been a lot of advances. We can take the amino acid sequence and predict what that's gonna look like using computational tools including artificial intelligence, but there is still nowhere near enough data and enough sophisticated understanding of why a certain amino acid sequence has a certain structure. Why are some protein structures more stable than others? Why do some fold up more quickly to the structure? Why do some have to go through partially folded states before they can get to their final active structure? It seems like nature and biology have evolved to really take advantage of the different ways that proteins can fold and the different states having different stabilities. We're finding out more and more that different [intermediate] states are not just random things that happen, but they actually can have important functions so that the protein cellular machinery recognizes ‘Oh, this is kind of misfolded? Let's get rid of that.’”


Out of the hundreds of thousands of proteins relevant to human health, the Jaswal Lab focuses on only a few. “One of the proteins that we look at is beta 2 microglobulin (β2M), which was an object of study in my postdoctoral lab at Yale. My postdoctoral advisor had chosen that to try to probe the dynamics of because it's involved in a disease called dialysis related amyloidosis. The interesting thing is that the protein normally is fine and behaves very well in people. But, in people who are on dialysis, over time this protein ends up aggregating into their joints. This leads to dialysis related amyloidosis. It's a very nice experimental system, because you can manage it under normal conditions, but you can also then induce it to do different things by approximating the disease conditions. When you're picking a system to study, you want significance, but you also want it to work in your experimental parameters. Another one that we study, protein L, is a bacterial protein that does have some biological importance because it binds to a protein in our immune system but we use that as really a test case as we're developing new ways to apply hydrogen exchange mass spectrometry; it’s one way to make sure that this method is giving us results that make sense. Because protein L has already been studied really well, and we know how it should respond and what its stability and dynamics are, then that gives us a good control protein to validate our method. Once we have the method validated, then we can apply it to other systems.”


In addition to focusing on the protein folding dynamics of β2M and protein L, the Jaswal Lab also tests new methods of studying protein folding under physiological conditions.

“Because the traditional methods of studying protein folding have required pushing the proteins out of normal conditions in order to destabilize them so that you can make measurements of how they're stabilized, a big focus of our work is developing methods or applying new ways to probe what's going on with proteins under normal conditions without harassing them with harsh conditions. It can get easy to get lost in the weeds of the specific experiments and method development; we have to apply computational simulations to be able to understand our data, so it's a big investment. We have to remind ourselves that big investment is because with the development of this method, it's going to enable us to access information about a lot more proteins than what can currently be accessed through methods that require that you beat up your protein and see how it recovers.”


Being Human in STEM


The Amherst Uprising of November 2015 inspired Dr. Jaswal to start HSTEM. The Uprising, organized by three Black women, was originally planned as an hour-long sit-in in solidarity with other Black Lives Matter protests taking place on other campuses and around the world.


“There were these huge protests going on that most of us had no idea about in South Africa, because tuition there had been raised, and [education] was going to be out of reach for a lot of regular students. There were these massive protests going on at campuses, especially University of Missouri. And so they said, ‘Okay, we got to do something. We got to do this sit-in in solidarity.’” The students made posters for the sit-in in Fayerweather, where there happened to be a Hampshire student who suggested they make the sit-in a Facebook event. When the sit-in began in Frost Library less than 24 hours later, there were hundreds of people there, and more kept coming.


In this video marking the five year anniversary of the Uprising, Christine Croisdaile, “one of the women who became a big mover behind the four day sit-in talks about sitting there. People said their prepared statements, but she felt that they had to do more, we have this whole attention. So she got up and said, ‘We can't just pretend that these things aren't happening at Amherst, too.’ She really opened the floodgates to students sharing what their experiences had been here at Amherst in our classrooms. It really just unleashed these pent up emotions and created space where people were listening. I and anybody else that I've talked to had never experienced anything like that before where people were talking and crying and raising their hand to get the microphone. Over that first day, up to 2000 people had come through the library. I just was so amazed and inspired and you can't replicate what that feeling was like. At one point, I saw the three women who had started it and I [went up to them and] said, ‘I'm so proud of you. I'm so inspired.’ One of them, Sanyu Takirambudde ‘18, said, ‘Thank you so much, and can I talk to you about being a woman of color in science?’”


Louise Atadja ‘16, who was taking biochemistry with Dr. J at the time, also spoke with Dr. Jaswal about her experience as a woman of color in STEM. Dr. J remembered her first biochemistry course meeting after the Uprising: “I said, ‘Okay, let's put away our handouts. This thing just happened. We need to talk about this. I want you to take five minutes to just write for yourself: What does the Amherst Uprising have to do with STEM? What does the Amherst Uprising have to do with me?’ [During the 5 year celebration of HSTEM,] Louise said that in writing that, she and the TA for the class Gaby Mayer ‘16 started talking; the Uprising does have to do with STEM, but [biochemistry was] one of the only STEM classes where we're even making space to talk about this. Louise and Gaby came to me and said, ‘We want to do a special topics class where we keep sharing these stories, go into the literature, but specifically about STEM.’”


Dr. J said yes, and ultimately nine students participated. “It was just incredible. We didn't know what we're doing. We just made it up as we went. And by the end, they made a web page for their projects.” These projects included annotating about 40 articles, interviewing 40 people at Amherst, and reaching out to 20 other liberal arts institutions about their efforts to support underrepresented students in STEM. “The students organized a community salon with project stations that was fantastic; there were over 75 people milling around. I thought, ‘This is something special. We need to keep this going.’ That was five years ago, and now here we are. There are 11 other institutions that are doing the class, and we're talking about Being Human at Amherst to bring it beyond STEM. STEM may be an easy target, but it is by no means the only discipline where being human and holding your identity [matters]. We all are suffering from a legacy of white supremacy. All of us and every discipline.”


Getting Involved


After hearing the story behind HSTEM, I asked Dr. J how students can become involved in HSTEM at Amherst. There was a J term Being Human in STEM course this past winter with 50 students, the largest ever. “It would be great if people would educate themselves about the history of the Uprising and Being Human in STEM. We will be having at least two cohorts of being human in STEM with 18 people per cohort next J Term. And if there's a huge demand, maybe we can expand it.”


In addition to having another HSTEM J-term course, Dr. J has grand visions for expanding the program beyond STEM. “We are hoping to do a Summer Institute with faculty and staff called Being Human at Amherst that would be an intensive five day experience to try to capture what the students have been through and what we do with the students.” The program would integrate student reflections and experiences so their voices are heard without the barrier of having to directly approach faculty and staff. “But, because there's so much good will, so many people really want to do the right thing and try to help but they don't know how and they're afraid and they don't want to make mistakes, they don't want to be called out. That doesn't excuse anybody for not taking responsibility. The more we can do to meet people where they are and call them in in a supportive way, but then also keep them accountable, the better. That's my overall vision for Being Human at Amherst.”


However, you do not need to take the class or participate in the intensive experience to get the Being Human in STEM experience. “HSTEM is really about reflecting on your own journey, and the connection between what you're learning and yourself and what you can do, and how you can be the best human you want to be in the world. That is something that's not limited to taking the class. During this moment, we all have this amazing opportunity to change the course of education, our future disciplines, our careers. Now is the time to practice at Amherst, nobody's ever going to be in this kind of diverse community again, so let's take advantage of being with each other and do our best, knowing there is no magic bullet for getting it right. Let's practice, let's challenge ourselves. Let's make mistakes and make it okay to make mistakes. Let's call each other in instead of calling each other out and being afraid. Let's all have the mindset that we can learn and grow. And of course, none of us knows how to do this, right? Because we've never had a chance. This is such an amazing opportunity, both to be at Amherst at this time, and in our nation, even the world. We're so connected, and it's so clear how we haven't gotten it right yet. That means that this is our chance to work on getting it right. We don't want to just sit and hope that things are gonna get better. That's not what we're here for. We're here to actually do the work. Then when we do the work, we find out, oh my gosh, this feels like being alive. This is what being here is.”


Additional Resources:


January 20, 2021 article by Katharine Whittemore Four Days in Frost That Changed Amherst Forever


Thursday, November 19, 2020 From Protest to Progress: Five Years of Being Human in STEM @ Amherst and Beyond (also linked in various places above)


2020 podcast interview 'Being Human in STEM' with Professor Sheila Jaswal - I'm a scientist, and ... (podcast)


2019 Amherst Black Alumni Weekend Panel with Black HSTEM students


2019 Article written by Dr. Jaswal describing the inspiration behind and how HSTEM has evolved over time https://www.aacu.org/diversitydemocracy/2019/winter/jaswal


HSTEM Website


2018 Documentary: The Voices of the Pioneers by Maeve McNamara ‘19


Digital Memorial for Amherst Uprising


Thursday, November 12, 2020 Alumni Reflections on the Fifth Anniversary of Amherst Uprising (also linked above)

This conversation between Amherst Uprising alumni begins with reflection on the fifth anniversary and the digital website and continues towards present-day challenges of diversity, equity, and inclusion at and outside the College.


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