by Danielle Tsougarakis, Bioengineering ’20; and Kate Panzer, Bioengineering ’18
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
This morning, we found out that we would be spending our last night in Kumasi in a hostel, which is equivalent to a dormitory at a U.S. college. We packed our belongings and moved into a hostel called “Complex Brunei,” which is an apartment-style dorm for upperclassmen, each room furnished with three beds, a closet, a full bathroom, and a table. We were all excited to get the student experience of staying in a hostel and compare it to the visitor housing at the KCCR guesthouse.
In the afternoon, we had the opportunity to visit the international community school (ICS), a high school founded on the philosophy of bringing competitive, Western-inspired education to Kumasi. A friend of our team member Dave currently works at ICS and suggested we come speak to the prospective college students at the school. That being said, we gave a presentation on how the college application process works in the United States to a group of 10th and 12th graders. After our brief overview, we split into small groups and answered individual questions students had regarding different types of universities, SAT/ACT scores, the importance of a strong essay, and other application essentials. Speaking with the prospective students here and motivating them to apply to American universities was a great experience. Sharing our own college application processes and stories with the students was a fun and engaging way to fuel their academic aspirations. After our well-received presentation, the whole team left feeling accomplished.
For dinner, we had a special surprise outing to a nearby Chinese restaurant, where we shared many different dishes and passed them around on a rotating glass platform. For some of the Ghanaians, this was their first time trying Chinese food, so it was fun to hear their reviews of all the dishes. Upon returning to campus, we continued our beloved tradition of team bonding by playing the Noun Game and card games.
by Kaila Helm, Biological Basis of Behavior ’20; Kathleen Givan, Bioengineering and Political Science ’20; Katharine Cocherl, Bioengineering ’20; and Hope McMahon, Chemical and Biomolecular Engineering ’18
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
We started our not-so-lazy Sunday with a late start. We enjoyed our last weekend breakfast, provided by the one and only Nana Yaa. A fan favorite is always the avocados and the Milo, which we know we will miss dearly when we get back to the States. Luckily, we all have our personal stashes we plan on bringing back. We all had the much-needed opportunity to do laundry and catch up on life errands. Once mid-afternoon hit, we all decompressed by watching the Ghanaian vs. Ethiopian National Football teams on the television in a nearby dorm. GHANA WON THE FIFA QUALIFIER AND THE CROWD WENT WILD!!!!!
The next thing on the agenda was our farewell ceremony and dinner. We were instructed to wear our Ghanaian clothing that had been made for us during the trip, but some of us had not yet received the alterations back from the seamstress. When Nana arrived, clothes in hand, it was exhilarating to see the final products and wear similar colorfully patterned clothes to our Ghanaian counterparts.
The meal was catered by our favorite kebab stand, along with drinks, tilapia, and banku (the classic combination). Many of the people who have contributed immensely to our trip were there, and we enjoyed good conversation and memories into the night. We were put to shame as we watched the children dance their hearts out, using more rhythm and soul than we would know what to do with. It was so nice to see the program come full circle. We all looked back fondly at the welcome ceremony, where all the faces were unfamiliar but kind. Fast forward to the farewell ceremony, and this time, we saw the same faces and smiles, but now we felt connected to the people behind them.
by Meagan Ita, Ph.D. Student in Bioengineering and GABE Co-President
Cancer is a disease that affects millions, and over the last several decades, researchers have delved deeply into the biological underpinnings of the disease in the hopes of finding a cure. One major discovery is that mistakes in your DNA “instructions” can lead to cancer by crossing the wires in your cellular circuitry, and researchers have developed amazing new drugs that can cause tumors to melt away by targeting these broken components. The problem though is that, most of the time, the tumors come back, and this is a huge barrier to cures.
For a long time, everyone assumed that the reason the tumors came back was DNA mistakes on top of the original mistakes, with these new mistakes blocking the activity of the anti-cancer drug. However, new work led by Sydney Shaffer from the Arjun Raj Lab at Penn Bioengineering, published this week in Nature, challenges this view by looking all the way down at individual cancer cells and seeing how they respond to these drugs on a cell-by-cell basis.
Sydney found that in melanoma, contrary to what researchers thought, it need not be a DNA mistake that leads a cell to become resistant to the drug, but rather a change in cellular identity. Just like your body has cells of all different types, like skin cells and brain cells, cancer cells appear to change between different types, but unlike in the body, cancer cells do it in a seemingly random and uncontrolled way, and the cells exploit this variability to allow those rare cells that have changed their type to survive the drug.
Here, we talk with Sydney about the inspiration, triumphs, and challenges she faced in her research.
What was the initial inspiration for looking at drug resistance in melanoma?
For the first two years of working on this project, we actually didn’t have a clear question in mind. I was just trying a bunch of different experiments with melanoma cells, and I noticed something that we found thought-provoking. Whenever we gave the melanoma cells a particular drug, they would become resistant at exactly the same point in time. At first, this may not seem unusual, but for example, if everyone showed up at a restaurant to eat lunch at exactly noon, you would guess this was not happening purely by chance. Maybe classes let out right beforehand? Or a big meeting? For the melanoma cells, we would similarly expect there to be a range of different times for the cells to become resistant, but instead it all happened at once.
This observation helped us figure out that the drug-resistant cells probably already exist before we treat them. It also got us curious about the particular processes that make the cells resistant, and we spent many lab meetings discussing this observation until one postdoc, Gautham Nair, suggested trying some experiments based upon the classical molecular biology experiments of Luria and Delbrück.
Who were Luria and Delbrück, and how did they influence your work?
Max Delbrück and Salvador Luria (below) were scientists who, in the 1940s, performed a clever experiment that demonstrated that bacteria become resistant to viruses through random DNA mutations. According to Wikipedia, Luria actually had the idea for these experiments while watching slot machines!
Their experiment was super simple: it was basically a statistical way to see whether cells “sense and respond” to a challenge, or whether they just passively get a mutation that lets some fraction of them survive the challenge, basically like Darwinian evolution. The idea is that, in the first scenario, there is no history: every cell has an equal chance to respond when challenged.
But in the second scenario, history matters in that if your great-grandparent was a survivor, then all your relatives would be too. If you could redo history over and over, then sometimes maybe your great-great-great-great-grandparent would be a survivor, and so you would get a whole bunch of survivors when the challenge came. Luria and Delbrück’s results showed that this second scenario was what happened with bacteria, providing the first evidence for genetic mutations in bacteria occurring in the absence of selection, and they both went on to win a Nobel prize in 1969.
Arjun actually had just lectured about these experiments in our graduate course on modeling biological systems. We adapted the same strategy and theory as Luria and Delbrück’s experiments for our work but applied it to melanoma and actually found a different result. Our experiments showed that resistance in melanoma does not arise through a heritable DNA mutation.
Based upon this work, do you have any ideas for how we might prevent resistance in patients?
Yes. The recommended dosing for many of these drugs is daily. Our work would suggest that something like interval therapy might be more effective, for instance, if you gave the drug for a few days, killed many of the tumor cells, and then stopped the drug. During the time that the drug is stopped, the cells that initially survived the drug (we call these cells pre-resistant) could then transition out of this cell state and back to a sensitive state. Then, when the patient takes the drug again, it would be more effective at killing the remaining tumor cells. Another idea would be to find drugs that are specific to the pre-resistant cells and give these drugs in combination with other targeted therapies.
Were there any “Aha!” moments while working on this project?
One of the most exciting moments of this research was when we first found the pre-resistant cells. Hidden among thousands of pictures of empty cells, we were shocked to actually see the rare cells full of brightly tagged resistance genes (below).
What were some low points in working on the project? Do you recall any specific moments that you just felt intellectually and/or emotionally stumped? How did you get through them?
Oh yes, there were definitely low points during this project. One that stands out to me specifically was this one Friday afternoon where I presented at lab meeting. At the time, I only had a little bit of preliminary data. One of the members of the lab asked me a series of questions about resistance: How many different drug doses had I tried? Could I just give a lot and kill them all? What dose of drug is relevant for patients? What about drug resistance? Was I really interested in? All reasonable questions to ask. However, this was really overwhelming to a first-year graduate student because it made me realize that I didn’t have a clearly defined project that I was working on yet. There were just so many different questions that I didn’t know where to start.
Ultimately, with Arjun’s guidance, I came to realize that this was part of the process of figuring out what my thesis project would be, and the vagueness of our ideas at this time was a great thing because it left me open to find a problem that I found really interesting.
At another point in working on this: I remember that we were clearly conceptually stuck. We had identified the rare cells, but it wasn’t clear how to find out if these were the same cells that become resistant to drug. I had an entire lab meeting where we discussed this concern and came to the conclusion that, without some connection between the cells in this state and resistance, the work would be very speculative, which felt unsatisfying to me. Unfortunately, there wasn’t a quick fix to this problem. We just ended up trying a whole bunch of different ideas and eventually one of our strategies worked out.
Were there any funny moments that stand out to you?
Yeah! I was 40 weeks pregnant as we were finishing off our first submission of the paper! As my due date passed, I was really feeling the pressure to finish everything. Each day, I was coming into lab and just hoping I wouldn’t go into labor yet! Actually, the members of our lab had placed bets on when the baby would be born. Fortunately, those who bet on a late arrival ended up winning, and we submitted the paper the day before my daughter, Julien, was born. I was actually still at the hospital when I got the e-mail that the paper went to review.
So even though it might seem like this project is checked off the list with a kick-ass publication, there are probably a bunch of unfinished ideas you have. So,what are you working on next? Will this project ever be “done?”
For sure. The list of unfinished ideas is very long, and some of the questions that came from this work are now being pursued by other people in the lab. Right now, I’m working on ways of measuring the length of time that individual cells remain in these different cell states.
Interested in sharing your research in Penn BE? Contact penngabe@gmail.com for an interview by GABE (Graduate Association of Bioengineers) and let us know!
by Ethan Zhao, Bioengineering ’19; and Jason Grosz, Bioengineering ’19
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
Today, we went to see how Kente cloth is made. Kente is a special ceremonial cloth, often woven with a story or message in the pattern. Our tour guide showed us several different kinds of fabric they use, including wool, polyester, and cotton, and demonstrated how they are threaded from the original material with a wooden, hand-operated machine. Next, he brought us to see the Kente cloth weavers at work. It was incredible to see the speed and skill with which the weavers passed the shuttles back and forth between the strands of fabric to create a pattern, while Ghanaian (and sometimes American) pop blared from their handheld radios. Finally, he showed us the land where plants like cacao trees and cotton plants grow. After the tour, we bought a colorful assortment of Kente cloths, bow ties, and wallets.
Next, we went to a series of wood shops to buy various carved wooden souvenirs and to practice our bargaining skills. As we stepped outside the bus, we were immediately surrounded by dozens of shopkeepers, not-so-gently coercing us to check out their own shops. Since there were no listed prices, the prices for everything bought were the result of bargaining. Shopkeepers would often present us with relatively high initial prices, only to offer us “discounts” since we were students or “friends” to make us feel like we were getting a great deal. Overall, it was an overwhelming but exhilarating experience to fight for a price on every good we bought.
by Kaila Helm, Biological Basis of Behavior ’20; Kathleen Givan, Bioengineering and Political Science ’20; Katharine Cocherl, Bioengineering ’20; Hope McMahon, Chemical and Biomolecular Engineering ’18; and Dave Pontoriero, Biotechnology MS ’18
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
Today was the day we had been anticipating since the start of our trip: Presentation Day! We presented our final projects to a room full of people from KCCR. Scientists and research assistants attended to hear more about the designs we had been working on all semester.
Our presentations were in the afternoon, so we used the morning to work out any last-minute details. Each group presented on its pediatric tuberculosis diagnostic, with each trying to come up with innovative devices that could be implemented in the future. Even more exciting, we had an opportunity to present our more short-term ideas for problems that undergraduate students could address themselves. Our prompt was to create a project idea that could be completed in one year by one to five undergraduates with low funding requirements. The question-and-answer session that followed our presentations provided a wonderful opportunity to be critical of our ideas and contemplate the limitations of our designs, while still posing new questions regarding what could or could not work in our proposed plans for implementation.
After a busy start to our day, we were eager to spend some time relaxing and reflecting on our academic experiences. We were amazed by the progress we made in the construction of our proposals. As engineers and individuals pursuing the STEM field we planned to create technology that could positively impact Ghana. Yet our presentations and the feedback we received were another source of evidence that we must continue to work on the ways in which our devices can be integrated into the Ghana’s current medical system. Nevertheless, we were proud to present all that we learned to such an insightful audience.
After a successful afternoon of presentations, we headed out to dinner to celebrate. We went to the same restaurant we went to two weeks previously. There was live music, dancing, and our new team favorite: grilled tilapia.
by Danielle Tsougarakis, Bioengineering ’20; and Kate Panzer, Bioengineering ’18
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
Today, we had our last clinic visit of the trip to Suntreso Government Hospital. We first heard from Nurse Cynthia all about the hospital roles of diagnosing tuberculosis and providing patients with the necessary medication. It was a really great discussion; whenever we had a question, Nurse Cynthia had an answer based on her forty years of experience with TB patients. We visited the Voluntary Counseling and Testing (VCT) Centre of the hospital, where patients can pick up their medication every month and receive more education about their respective conditions. Nurse Cynthia discussed issues surrounding tuberculosis, including stigma about the disease, as well as educating the public on the symptoms and concerns surrounding the disease.
Afterwards, Dr. Thomas came and talked to us about HIV and other sexually transmitted diseases in Ghana. He described the prevalence, as well as prominent issues encompassing the diseases. Interestingly, the clinic only provides free condoms for people infected with HIV and not other sexually transmitted diseases (STDs). Dr. Thomas informed us, however, that despite the availability of condoms, they are often neglected for their intended use. Evidently, it is quite common for Ghanaians to repurpose condoms as fire starters, parasite protectors, and even jewelry. After our engaging discussion, we briefly viewed the STD clinic on site. Then, we headed back to KCCR, enlightened by the creativity of the innovative mind. We spent the rest of the afternoon refining our final presentations and projects. Then, we headed to bed for a good night’s rest before the big day.
by Kaila Helm, Biological Basis of Behavior ’20; Kathleen Givan, Bioengineering and Political Science ’20; Katharine Cocherl, Bioengineering ’20; Hope McMahon, Chemical and Biomolecular Engineering ’18; and Dave Pontoriero, Biotechnology MS ’18
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
We started off today by visiting a disease control center at Manhyia District Hospital. It was interesting to hear how they distribute monthly doses of their TB drugs. Unlike some of the other clinics we have visited, they had not received any pediatric TB as of this year and felt that TB was confined to highly populated communities within their district of 300,000 people. Although HIV is still an urgen issue, it was nice to hear a little bit of good news. We visited their lab, where they process their smear microscopy samples. For any multidrug-resistant (MDR) TB cases, they must refer their patients to KATH, which has better facilities to treat these patients. We then got to talk to the hospital’s only pediatrician in the newly built children’s ward. However, the hospital still experiences space issues that prevent mothers from staying in the same rooms as their newborns and that cause some children to be placed in the adult ward.
After our visit at the hospital, we began an exciting afternoon of activities. The program coordinator Nana Yaa planned a scavenger hunt of 10 items that we had to find in Kumasi’s large market before coming back to campus by tro-tro. We split into four groups and set off into the crowded streets in search of items such as bananas, something black, a picture with a kayayei, an ingredient for dinner, and a few other things We met several people along our journey. The vendors throughout the street were very friendly, wanting to help us find the goods we were looking for. We got to practice our Twi and we made several people laugh as we asked them for bankye kakro, a small fried ball made of cassava.
The team then went back to the guesthouse and shared everything that we purchased. The guys got live crabs for their dinner contribution, so everyone had a good time helping with the preparation. The competition resulted in a four-way tie (we’re all winners!!!) , and we went out to an outdoor barbeque restaurant for our celebration. Everyone got tilapia and banku, making it one of the best meals of the trip thus far. We then took a scenic tour around Kumasi for a bit and finally met back up at the guesthouse for ice cream and stories.
by Ethan Zhao, Bioengineering ’19; and Jason Grosz, Bioengineering ’19
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
Over the course this trip so far, we have been learning about how doctors assess and diagnose patients with tuberculosis in different settings. Today, we took a look at the system in place to ensure that patients adhere to their medications once the diagnosis occurs. We visited one of the 11 directly observed treatment, short-course (DOTS) center at Afrancho Health Center in urban Kumasi. The facility had about 50 employees and relatively limited resources for treatment other than a maternity ward and a small lab for diagnosing malaria. Instead, as the name suggests, it directly observes patients taking pills for the first week of treatment. Afterward, a trusted relative is brought in and educated about the dangers of breaking the regimen, to aid the patient in adherence. The DOTS center employee then follows up with each of the patients in their own homes at least twice a month to ensure they are adhering to their medication. We were surprised to learn that the social workers didn’t even consider tuberculosis one of the Top 10 most threatening diseases in the area, which included diseases such as malaria and HIV. However, this may be a testament to the effectiveness of tuberculosis education and treatment in this area of Kumasi, rather than evidence that tuberculosis isn’t threatening.
After returning from the DOTS center, we spoke to employees of the Kumasi Center for Collaborative Research (KCCR) about concerns we have about our projects. One person we spoke to is a data analyst who collects and analyzes data about the burden, distribution, demographics, etc., of TB across Ghana. We discussed how our idea of a phone application to process cough sound-bytes could contribute to data analysis and collection in the fight against TB. We also spoke to employees familiar with biological sample collection and preparation to help us assess the feasibility of our proposed devices.
by Kaila Helm, Biological Basis of Behavior ’20; Kathleen Givan, Bioengineering and Political Science ’20; Katharine Cocherl, Bioengineering ’20; and Hope McMahon, Chemical and Biomolecular Engineering ’18
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
Although we were supposed to visit a government hospital today, there was a bit of a mix-up. The person we were supposed to meet with had been sent out on another assignment. But no fear — we rescheduled that part of the saga for Thursday.
Instead of going straight back to KCCR, we headed back to the major market. On the car ride, a few of us wanted what we thought were fried coconut balls. After Nana Yaa flagged down a street vendor from the bus, she demonstrated her cardio fitness as Uncle Ebo kept up with traffic, and she was left behind with the vendor. It turns out our snack was raw coconut served with a side of fried cassava dough balls. We decided they tasted like coconut hash browns and were definitely worth the whirlwind experience. Thanks again, Nana Yaa!
Once at the market we split into two groups. Most of us hadn’t ever been in a more crowded place, between the goods and the people. We took a tro-tro for the first time and the highlight was buying all of the roadside snacks along the way. We got tiger nuts, plantain chips, meat pie (which tasted like pop-tart crust), fish pie, spring rolls with beans, and peanut butter cake (which was actually brittle). The rest of the day was spent working on our academic presentations.
We ended the day by working on a component of our final project: selecting small side projects appropriate to be tackled by Penn undergraduates. The overarching aim is to give back to KCCR and Ghana, as both have given us so much during our stay here. Our professor structured the activity like an elimination tournament, giving us “money” to fund projects. The four projects with the most money at the end of the night survived to the next round, while others were eliminated. Stay tuned to see what we have come up with!
by Danielle Tsougarakis, Bioengineering ’20; and Kate Panzer, Bioengineering ’18
David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.
Without any planned activities for the day, the entire group decided to attend church to gain a better understanding of a Ghanaian Christian service. We ended up going with Uncle Ebo (the driver for KNUST’s School of Public Health, loved by all) to the Church of Christ–Oforikrom. Through joyous singing and colorful garb, we were all able to appreciate the experience regardless of individual religious beliefs.
Once we returned back to KCCR, we cooked breakfast for ourselves, making “toad in a hole” (an egg cooked in the center of a piece of bread) and raving about the delicious local sugar bread, peanut butter, bananas, and pineapple. What a satisfying meal!
After a few hours of enjoying our relaxing Sunday morning, we headed via taxis to the Kumasi City Mall! Here we people-watched and enjoyed the modern ambiance of the bustling stores around us. We even got ice cream from a popular ice cream shop — “Yah!” We made a much-needed run to the grocery store to stock up on our new Ghanaian favorite, Golden Tree chocolate. Afterward, a few students tried a Virtual Reality stand and enjoyed the thrill of a roller coaster from the comfort of their seats in the mall. Later in the evening, the group spent some time working on their academic journals among other projects. After a full day, we finished up the night with a tasty dinner of a popular local noodle dish called indomie.