Brenda Cesar

Research Lab: Y. Kim

Zipping up chromosomes

At the beginning of meiosis, chromosomes need to replicate their DNA and find their homologous partner. This pairing is then reinforced by the formation of a zipper-like protein structure called the Synaptonemal Complex. This complex was first seen in crayfish spermatocytes in 1956. Since that time, this complex has been visualized in a diverse range of eukaryotic organisms such as fungi, nematodes, plants, and mammals. It is recognized as a meiotic hallmark that defines the stages of prophase I. Without proper assembly, homologous chromosomes can lose their physical linkage with one another and separate prematurely, leading to an incorrect number of chromosomes in gametes. Despite the conserved role and appearance of the synaptonemal complex, little is known about exactly how these proteins interact with one another and the mechanism behind their assembly and disassembly.

The Yumi Kim lab uses a combination of biochemistry using purified components and cytological analysis in the nematode C. elegans, because it is a widely used model organism for studying meiosis. A great advantage of this organism is that it allows us to visualize meiotic progression and chromosome dynamics in a spatiotemporal gradient in a single gonad. During these past few years, our lab has been able to identify missing components of the synaptonemal complex. Identifying these components has allowed us to reconstitute the complex in vitro for the first time in any organism using a bacterial protein expression system.

My project aims to use this reconstituted complex to address long-standing questions such as what is the stoichiometry of their components, how do these proteins interact with one another, and what is their assembly mechanism. I am fortunate to be in a lab that has allowed me to work on a project that interests me and has given me the training I need to become a successful scientist. During these past few years, I have received ample training in biochemical techniques outside and within Hopkins, I have written training grants with the help of my PI, I have collaborated with other labs in the program, I have trained undergrads and rotation students, I have attended national and international conferences, and I am currently receiving training at the Johns Hopkins School of Medicine to learn how to do cryoEM on my complex. I urge students to choose a program and a lab that not only fosters their scientific interests but also propels and challenges them to learn new topics and techniques to achieve great science.

Integrating cell biology and biochemistry

Our lab is evenly split between people who work directly with worms or do biochemistry. This kind of approach where cell biology is integrated with biochemistry is what allows us to do great science. It is not only about what happens to proteins inside a test tube but also about what happens to the proteins in their biological context when they are inside the cell.

My PI is an incredibly passionate scientist. She is so inspiring because she works harder than any graduate student in the lab. Whenever she learns about a new topic or technique, she starts reading many papers to get familiarized with the subject. She still has her bench in the lab and works on experiments almost every day. When she is not on the bench, she will be furiously running AlphaFold predictions on all the meiotic proteins that we study. She is a great mentor who has helped me get better at presenting my data, analyzing and conceptualizing my results, and improving my writing. She actually began the project that I am currently doing when she was still a postdoc, and I am grateful that she placed confidence in me to work on it and has supported me every step of the way.

CMDB program

I completed my Bachelor’s degree at the University of Puerto Rico – Rio Piedras Campus. Every Wednesday during my undergraduate years, universities from all over the US would come and talk to us about graduate school opportunities trying to convince us to apply. On one of those Wednesdays, Dr. Steven Farber and a graduate student came to talk to us about opportunities at CMDB. I vividly remember being so impressed with the quality of the talk and the honesty that was coming from them. I knew that I had to apply. During that year, I applied for a summer internship and was ecstatic about getting a place in that year’s cohort. That summer, I learned so much about FRET and droplet formation assays, and my mind was opened to the world of biophysics. After having such a nice experience, I decided to apply to graduate school in CMDB.

CMDB is an interdisciplinary program where I knew that I would have the opportunity to learn a wide range of topics from developmental biology to biophysics. This breadth has helped me not only by motivating me to expand my scientific knowledge but also by preparing me for any challenge that I come across. I can attend a cell biology or biophysics seminar, and I feel confident that I can follow through the talk with ease.

I like that it is a highly collaborative program, where I can just Slack or email anyone, and people are willing to help out with a problem I am having. During my third year, I easily set up a collaboration with Dr. Stephen Fried, where all I had to do was send him an email expressing my interest and motivation for setting up a collaboration and we got to work almost instantly. His help in mapping the protein-protein interactions within my protein complex using crosslinking mass spec (XL-MS) has been indispensable in my project. Most of the people in the program are in the same building complex so I am always running into people, and I enjoy catching up on their science, life, and pets. Someone is always willing to lend a reagent for an experiment, help with a protocol, or just be willing to talk about scientific results and theories.  

Plenty of opportunities

Johns Hopkins University is a research-focused institution, which means ample opportunities for mentoring and teaching undergraduate students abound. I can help TA or work in the lab alongside passionate undergraduate students. It is a highly rewarding experience because you get to see them get excited about science for the first time, even if it is just looking at a green tube filled with expressed GFP. Someone once took the time to teach me. Now, I can give back and help undergraduate students pursue their goals and dreams and train the next generation of scientists.

After graduation, I plan to take a non-academic path, and my current goal is to work in biotech. Being at Hopkins, I can reach out to the wide network of alumni and seek advice. The Doctoral Life Design Studio is always available to help students with crafting cover letters and CVs, sending internships and career opportunities, and helping students set up goals and strategies to be successful. I regularly participate in their biotech and biopharma industry career days and workshops, where professionals from a wide range of jobs give talks about their scientific journey and the characteristics that employers are looking for. Similarly, the CMDB program also offers Career Friday events to learn more about unconventional paths after completing graduate school.

Life in Baltimore

Baltimore was not my first choice of city, because it does not have the best reputation. However, after having lived here for a few years, I can now call Baltimore home. It is an incredible city with lots of personality and quirkiness. I enjoy the proximity to the city while also being close to nature. A walking trail, that I enjoy after stressful days in the lab, is close to my home. The upside of Baltimore being such a connected city is that I can easily travel to other cities such as Washington DC to watch the cherry blossoms, go to New York to attend a concert, or go to visit Virginia to hike. Baltimore is also full of small communities for music and art enthusiasts. One of the best pastimes that I have started in graduate school is joining my local pottery community. Although it was very challenging at first, people were willing to teach me their tips and tricks until I eventually got better. This kind of attitude speaks to the type of people who can be found in Baltimore.