Advisor: Kaihang Wang
Current Research: The field of synthetic biology is advancing as DNA sequencing and synthesis technologies enable larger scale cellular modifications. But this raises the question, what should we build? Part of my work at Caltech is centered around advancing mega-base scale genome engineering methodologies. Such technology has recently been used to create an E. coli strain, Syn61, that has had its DNA fundamentally changed by removing all instances of 3 codons from its entire protein coding genome. These codons can be reassigned to incorporate unnatural amino acids with novel functions into designer proteins. My lab's genome engineering techniques are also being employed to create an E. coli strain with a minimized genome that has nonessential genes removed. The product of this work would be a simpler microbe for biological study that can also be a better platform cell for biotechnology applications. As synthetic biology develops, we will eventually employ microbes to perform complex tasks from bioremediation to energy production to living medicines. In an attempt to enable this, smarter cells need to be created, so part of my work is dedicated towards developing synthetic circuits to direct complex transcriptional and translational networks based upon a variety of input signals.
Why Bryan chose Caltech: "I chose Caltech because it had a research atmosphere that I believed would be the most conducive to PhD work. The small size of the school lends itself to hiring few faculty, which also means the faculty that are here are those leaders in their respective fields with unique ideas which set them apart. This fact led me to find professors during my interviews who did something truly fascinating, as opposed to them simply being "in my field." Here, as opposed to other top tier schools, I felt that I could email any professor and they would agree to have a 30-minute chat with me over lunch, and that their success didn't lead to an overinflated egos. The limited number of faculty meant each professor knew what others were working on and likely had some connection with all of them, which ultimately leads to a much more collaborative environment than other schools."
What about biotechnology (or micro/nanomedicine) excites you? "Biotech is the exciting intersection between business and biology. It is sometimes hard as a scientist to figure out where your work figures into the greater biomedical community. Considering the biotechnology implications of a certain idea helps biologists ideate in the translational field. The part of biotech that excites me the most is that my seemingly purely scientific idea can eventually help people in need."
Elena Kim Perry
Advisor: Dianne Newman
Current research: Since the discovery of penicillin in 1928, environmental microbes have been appreciated as an important source of medically-useful antibiotics and other drugs. Antibiotic-producing microbes have also been used for biological control of crop diseases, and thus hold promise for improving agricultural sustainability. Yet at the same time, microbial production of natural antibiotics may sometimes lead to undesired consequences for humans, such as increased rates of pathogen resistance to clinical antibiotic treatments or suppression of beneficial soil microbes that promote crop growth. In order to develop a predictive understanding of when and how natural antibiotics benefit or harm human health and agriculture, Elena is characterizing microbial responses to a widespread class of bacterially-produced antibiotics called phenazines. In particular, she is studying the impact of phenazines on the evolution of clinical antibiotic resistance, as well as the structure and composition of wheat-associated microbial communities. Elena completed her undergraduate degree at Yale University, where she majored in Ecology & Evolutionary Biology and was awarded the William R. Belknap Prize for Excellence in Biological Studies for her senior thesis. She also received a Fulbright research fellowship to study how conservation practices affect the gut microbiome of a highly endangered New Zealand parrot, and an NSF Graduate Research Fellowship to support her work at Caltech.
What non-academic accomplishment are you most proud of? "When I was an undergrad, I learned how to play an instrument called the carillon, which consists of two dozen or more large bronze bells in a bell tower, mechanically connected to a manual keyboard and series of pedals. As a member of my university's student-run group of carillonneurs, I had the opportunity to travel and play carillons located around the US and Europe, and in my senior year, I passed the practical exam to join the Guild of Carillonneurs in North America. Unfortunately, there is no carillon near Caltech, but I hope to have the opportunity to play the carillon again in the future."
What about biotechnology excites you? "Biotechnology is a unique field in that it interfaces with so many of the biggest and most fundamental problems facing humanity today, from developing treatments for infectious diseases and chronic health disorders, to promoting food security, to mitigating climate change and improving environmental sustainability."
Nicholas S. Sarai
Advisor: Frances H. Arnold
Option: Biochemistry & Molecular Biophysics
Current research: Many of humankind's great achievements in the past centuries have been due to the classes of molecules we have created – pharmaceuticals, fuels, and materials included. Unfortunately, many of these molecules persist in the environment and cause harm. One of the great challenges for the next century is to develop ways to degrade harmful chemicals, or even better – to convert waste molecules into new products. Enzymes, the catalysts responsible for all life, catalyze a dazzling array of reactions in Nature – doing so in aqueous solvent under ambient conditions. Directed Evolution, the iterative process of mutating proteins, testing for function, and selecting improved variants has been proven to endow enzymes with functions that they are not capable of natively performing. In the Arnold Group, Nicholas is using Directed Evolution to tailor various classes of enzymes to perform non-natural chemistry to degrade and valorize anthropogenic compounds. Nicholas received his undergraduate degree in Biochemistry from the University of Denver. Before coming to Caltech, Nicholas spent two years at the National Renewable Energy Laboratory in Golden, Colorado where he studied the biomass deconstruction enzymes of (hyper)thermophilic bacteria and engineered them to produce fuel molecules from lignocellulosic feedstocks.
What about biotechnology (or micro/nanomedicine) excites you? "The growth in human capabilities and economies over the last two centuries has been coupled to a less welcome growth of our impacts on the Earth system. My overriding goal is to use biology's toolkit to stem some of those impacts. Take for example the teeming diversity of species throughout Earth's terrestrial and marine biospheres that have evolved to grow without immediate impact, nowhere more obvious than the exquisite feedback loops in the biosphere that have historically regulated climate. If only we could do the same! I am hopeful that harnessing the properties of life such as evolution and self-replication and scaling them via biotechnology can empower society to uncouple growth and impacts on our planet."
What are you most looking forward to as you participate in the BLP at Caltech? "I have had relatively little experience in my early scientific career in understanding how industrial science is conducted. Making a positive impact through biotechnology requires consideration of complexities outside the scope of scientific knowledge alone including the pathways to development, commercialization, and deployment. I am excited to gain perspective on these important facets of biotechnology and anticipate that the BLP will ground this perspective and open potential for making an impact via biotechnological innovations."
Advisor: Tom Miller
Current Research: Nucleic acids for uses in molecular programming, nanotechnology and therapeutics can be designed based on their secondary structure. However, the current models for the secondary structure are incomplete and obsolete in some cases. To fill the gap, we are developing new computational models to better parameterize RNA and DNA. Marta received her undergraduate degree in Chemistry from the Autonomous University of Barcelona in 2018. She is currently pursuing a PhD in Chemistry at Caltech, supported by the La Caixa Fellowship for Postgraduate Studies.
Why Marta chose Caltech: "I was introduced to Caltech as a place where individuals have a passion for science and interdisciplinary collaboration. In my experience, this has proven to be true, and I am really enjoying my current collaboration with a lab from another division. Caltech has a tight knit community where it is easy to belong."
What Marta is most looking forward to as she participates in the BLP at Caltech: "In the BLP, I am most looking forward to meeting alumni and young professionals in different biotechnology companies and learning about incoming fields and technologies."
Current Research: Single-cell RNA sequencing allows researchers to understand the transcriptional profiles of cells, and with efficient methods, minute changes in expression can be identified. Current single-cell RNA sequencing methods can be inefficient, and those available in commercial kits are compatible with only mammalian cells. In an effort to make single-cell RNA sequencing applicable to more cell types with increased efficiency, Sarah is trying to use microfluidic devices and chemical capture to work on a new protocol. Sarah also has an interest in translational research and is helping with the RNA capture aspect of a viral diagnostics project. Sarah received a B.S. in Chemistry from Carnegie Mellon University in 2019.
What is one thing we would be surprised to know about you? "In college, I was in three chemistry themed musical murder mysteries."
Why Sarah chose Caltech: "Most of why I chose Caltech can be tied back to atmosphere. The small size and encouragement of interdisciplinary research facilitates collaborative work. The option to explore research opportunities in any department was also important to me as my interests lean towards the application of chemical and biological research, which can be found across science and engineering departments. Caltech offers such great scientific opportunities, but social health was also a factor I considered when deciding on graduate school. When I visited here, the students seemed genuinely happy with their lives, both research and extracurricular."
Advisor: Mikhail Shapiro
Current research: While optical imaging enabled fundamental breakthroughs that substantially advanced our understanding of biological processes, this technique is hindered by it's inability to penetrate deep inside the body. Unlike optical imaging, ultrasound can penetrate centimeters deep into tissues while maintaining a high spatial resolution. To capitalize on these unique properties of ultrasound the Shapiro lab is focused on engineering gas vesicles (GVs), hollow protein nanostructures derived from buoyant microbes, as the first genetically encoded imaging agents for ultrasound. Shirin's goal is to engineer GVs as genetically encoded ultrasonic markers of cellular activity. In her first project, she is using GVs to track and control the activity of T-cells inside the body. If successful, this tool will enable T-cell tracking with high spatiotemporal resolution during immunotherapy, as well as ultrasound-guided local destruction of T-cells that display off-tumor activity. In her second project, Shirin is developing GVs that respond to neural activity, with the vision of enabling whole-brain functional imaging. In the long-term, she hopes to establish a powerful paradigm for noninvasive in vivo imaging of cellular activity deep in our body.
What is one thing we would be surprised to know about you? "Having finished my high school in Iran, I chose a track that had no exposure to biology. Therefore, during my undergraduate studies at MIT, I enrolled in an introductory biology course during my first semester, and as much as I was fascinated by the topics, it was the hardest class I had ever taken. After struggling with biology in my first year, I decided to leave biology out of my curriculum for the rest of my studies. I graduated with a B.S. and an M.Eng. in electrical engineering and computer science, but eventually found my way to back to biology by combining it with topics that were in my comfort zone. Today, I'm a second year Bioengineering graduate student, working with biology every single day. Everything comes back together at the end!"
Why Shirin chose Caltech: "Before starting graduate school, I had mostly worked in biotech labs at MIT. Still, during the graduate school interview process, I realized that I still needed to develop a much stronger foundation in biology. Caltech was the best place to achieve that goal while still working on developing exciting technologies. Caltech also provided me with a chance to build strong connections with faculty and find remarkable mentorship. Also, I can't deny it… it's hard to say no to sunny California!"