Sometimes life tells us we鈥檙e meant to do something. In Camila Sousa鈥檚 case, it started young, growing up in a house in Boulder with not one but two PhD scientists for parents. Camila鈥檚 mom is a molecular biologist, and her dad, Marcelo Sousa, is a principal investigator here in the Biochemistry Department. Camila is in her Junior year, pursuing dual majors in Biochemistry and MCDB, and working in the esteemed Cech Lab on DNA methylation enzymes.
Choosing CU Biochem
Camila remembers hearing her parents talking shop often as a child. She doesn鈥檛 describe their influence as pressure, but rather as fostered curiosity: 鈥淚 was always interested in what they were discussing. Growing up I鈥檇 always wonder how things worked at a molecular level鈥攁nd my parents would quickly explain.鈥� Camila wasn鈥檛 satisfied with the answers she got and decided to follow in their footsteps. 鈥淏iochemistry is the best approach to our molecular understanding as it relates to biological processes.鈥� She鈥檚 quite matter of fact in saying this, almost as if she鈥檇 been raised by scientists.
As a born and raised Boulderite, Camila decided to stay true to her roots and enroll at CU, where she says she鈥檚 glad to avoid paying rent. However, perhaps most enticing were the ample research opportunities available through the Biochemistry department: 鈥淭he research opportunities at CU Biochem were much more independent than other programs鈥攔eal independent research opportunities versus a more railroaded experience assisting on someone else鈥檚 project.鈥� As for out of state options, Camila felt that spending twice the money on tuition wasn鈥檛 worth the potential added value. Instead, Camila followed in her parents鈥� footsteps and decided to major in both MCDB and Biochemistry, choosing the two for their complementary approaches to similar subject matter.
For example, after taking immunology this past semester, which is an MCDB class, Cech Lab held a journal club where she learned about a specific receptor involved in immune responses. 鈥淭he paper in our journal club focused on the structure of the protein and how it interacts with nucleic acids, whereas the MCDB paper focused more on the protein鈥檚 enzymatic cascade and broader cellular effects.鈥� Even with the continued support from home, transitioning from high school to college was a big step for Camila. The increased independence presented a major challenge to overcome:
鈥淵ou have to want to learn, want to do well, be generally interested in what you鈥檙e doing. It can be a challenge to figure out your learning language鈥攈ow you want to study to get the information you need. Study habits were probably the most difficult to figure out. Also, questions鈥攜ou have to go to the professor, they won鈥檛 be on your back checking if you understood. I have a free tutor in my parents, but I鈥檝e noticed a different approach now that I鈥檓 in college鈥攖hey鈥檙e forcing me to think for myself more rather than feeding me information.鈥�
Conducting Research
Camila鈥檚 favorite classes thus far have leaned toward her father鈥檚 favored discipline. Though she hasn鈥檛 taken many upper-division courses yet, her favorite thus far has been Principles of Biochemistry. As with other Biochem majors, as an underclassmen Camila鈥檚 schedule focused on foundational Chemistry, Biology and Mathematics to prepare her for the integrative nature of biochemistry. When it came time to take Principles, Camila enjoyed how the course brought things together, remembering focusing on the various instruments that populate biochemistry labs, learning how they work and how typical workflows produce data. She also flourished in Molecular Cell Biology 1 which centered on the Central Dogma of Biology: DNA replication, transcription, and translation. 鈥淚 liked this class because it started getting to the edge of our knowledge in that field. The professors wouldn鈥檛 have answers to the questions we鈥檇 ask.鈥� Camila had found her home pressing the frontiers of human understanding, in exploring those childhood questions her parents never quite answered.
Soon unsatisfied with the answers to her big questions available in her lectures, Camila decided she would pursue research. She started by volunteering in her dad鈥檚 lab, doing inventory, organizing chemical shelves, and doing odd jobs for grad students. Camila (charitably) describes it as 鈥榞etting acquainted with the lab,鈥� not really research, but a foot in the door.
If you鈥檙e interested in research, get into a lab in whatever way you can. I started off doing inventory and cleaning the fridge, because I really wanted to get into a lab!聽I started emailing professors the summer between freshman and sophomore year, so not a ton of class experience. I shared my class experience, my majors, and told them I was interested in their work.
Today she鈥檚 in the Cech lab, which focuses on RNA biology. Camila is currently assisting a post-doc working on chromatin-associated proteins鈥攎odulators that indirectly control gene expression by modifying the molecular structure of the chromosomes that house our genes. Camila鈥檚 project is specifically focused on DNA methyltransferase 1 (DNMT1), an important enzyme responsible for methylating DNA that her postdoctoral mentor previously identified. Methylation is the process of attaching a methyl group to a specific site on a gene where it can affect transcription鈥攗sually blocking it. We call this process epigenetic because it presents an indirect way of affecting the Central Dogma, namely transcription, without modifying the specific nucleotide sequence of our genetic instructions. As Camila reminds me, it鈥檚 also a dynamic process, 鈥渢he gene in question can be methylated or de-methylated whenever it needs to be activated.鈥� Camila鈥檚 day-to-day includes synthesizing the RNA transcripts her team has identified as interacting with DNMT1, while preparing for upcoming binding studies between the RNA and the methylating enzyme, which she says will provide a better picture of what the interactions look like.
Why is DNA methylation so important? Abnormal DNA methylation patterns are found in many cancers. According to Camila, in some cancers there is a pattern of dysregulation preventing DNMT1 from methylating appropriately, meaning cell cycle checkpoints can be missed, anti-tumor factors are ignored, and cancerous cells begin dividing unchecked. Quantifying exactly how these compounds interact can give us greater insight in how these abnormal methylation patterns come to be, making Camila鈥檚 work foundational to developing targeted therapies. Importantly, as biochemists work to decode the machinery responsible for DNA methylation, we move closer to developing bioengineered treatments for all genetic disease with sequence specificity. For instance, imagine targeting the mutated hemoglobin-Beta allele (responsible for Sickle cell anemia) for methylation while allowing the other copy to continue producing healthy red blood cells, all while harnessing the human body鈥檚 own cellular machinery.
Looking Ahead
Beyond her world of RNA-oncology, Camila is excited where biochemistry as a field is heading. She excitedly tells me about some technology in development her father shared with her:
Right now, we don鈥檛 have a method of figuring the structure of a protein based on its amino acid sequence even though it represents the totality of the code. However, Google is working on a machine learning program [AlphaFold] that can predict and visualize protein structure based on the amino acid sequence alone. I haven鈥檛 worked with structural biology yet, but structure is quite difficult, especially for insoluble proteins like membrane proteins. It can be a challenge to purify, difficult to work with lots of subunits, so this would be a major boon to the field.
A boon indeed, as the author鈥檚 own research would benefit immensely from this sort of plug-and-play amino acid decoding. Once scientists can consistently predict protein structure, we move closer to predicting interaction and function. Google鈥檚 technology may eventually allow scientists to circumvent expensive experimental methods for determining protein structure, like X-ray crystallography and cryo-election microscopy, entirely.
Though Camila hasn鈥檛 had as much free time given her ongoing research, she used to be an avid ballet dancer, taking classes and performing with her troupe 鈥渙nce in a blue moon鈥�. Aside from ballet, both of Camila鈥檚 parents were born outside the U.S. (dad is Argentinian, and mom is from Germany), so she鈥檚 had ample opportunities to see the world: 鈥淚 got to go to Italy for ten days around 2018鈥攚e started in Venice, looped north, then ended in Rome. We had two full days to do nothing in Venice, and by the end it felt like I鈥檇 seen everything twice! I loved going to the historical sites, that鈥檚 part of why I love traveling.鈥� Unfortunately, COVID has put both travel and research plans on hold for the time being. In the meantime, Camila continues to plan her next round of experiments and life after Boulder. She鈥檚 thinking grad school, almost certainly in Molecular Biochemistry, but she hasn鈥檛 settled on a topic beyond human health. Wherever she goes, Camila wants to continue exploring the mechanisms behind human diseases. We鈥檙e excited to see where Camila鈥檚 research eventually takes her, as she鈥檚 sure to make a big splash wherever she lands.
