Advisors: Kaihang Wang and Richard Murray
Current Research: The typical modality for using engineered cells is to employ a homogenous population of cells, with each cell providing the same function. However, many applications could be substantially optimized through coordinated use of heterogenous cell population (a consortium), with each population subset performing a distinct function and combining with other functions synergistically. For instance, a microbial infection in the gut could be disrupted by introducing a consortium with members that produce antimicrobial peptides, sequester essential resources, among other functions. Nonetheless, the use of consortium raises several questions, chief among them; how do we precisely and consistently control consortium composition? My current research focuses on implementing one such answer to this question. This answer exploits the ‘bugs' (or features) inherent to biological systems, including stochasticity and the unique dynamics resulting from finite resource pools.
Why Matthieu chose Caltech: " I visited a couple schools and when I came to Caltech I was astonished by how passionate the students were about their research and labs! Further, my research interests have always lied at the interface of modeling and experiment, and Caltech is one of the few institutions that truly approaches biology from this interdisciplinary perspective. Finally, the size of Caltech was very appealing to me as it meant a much tighter-knitted community, strongly enabling collaboration within and between the various divisions."
What non-academic accomplishment are you most proud of? "In undergrad, I worked up my one rep max for my bench press to 225 pounds despite only weighing in at 155 pounds myself. Currently back down to 185 because of an injury, but working back up to surpass that 225 record!"
Advisor: Niles Pierce
Current Research: Nucleic acids are highly programable macromolecules based on their secondary structures. The CRISPR/Cas technology is a versatile platform which enables researchers to attain gene manipulation ranging from bacteria to human. Programable guide RNAs (gRNAs) play a central role for their abilities to direct Cas effector proteins onto target genes of choice. The Pierce Lab developed conditional guide RNA (cgRNA) to achieve spatiotemporal control of CRISPR/Cas activity based on programmability of gRNA. Heyun is currently working on optimizing the system and enabling the detection of endogenous RNAs. This work will enable countless applications from targeted gene therapy to environmental surveillance. Heyun received her undergraduate degree in Chemistry from Peking University in 2019.
What is one thing we would be surprised to know about you? "I took classes on Cultural Relic Repair and Conservation during my undergrad study, during which I have repaired 5 pottery ear cups from the Han dynasty (~1800 years ago). Fun fact: I needed to dig and clean shattered pieces in the mud and glue them together for a complete shape – but the red paints on them are still bright and well preserved even after such a long time."
What are you most looking forward to as you participate in the BLP at Caltech? "I am excited about transitioning scientific research from lab into the world, but my previous trainings have taught me little on this. I am looking forward to knowing how to do so in the BLP. I am also looking forward to meeting people in biotech companies as well as peers with similar interests."
Advisor: Kaihang Wang
Option: Chemical Engineering
Current Research: It is evident that viral infections are complex processes that include many steps and interactions with different cellular structures. These interactions are dynamic, and furthermore, new viruses surface making the studying of viral replication and infection processes extremely important. Therefore, the motivation behind this project was when we raised the question of how do we detect and track viral infection and replication? Current methods rely on direct manipulation of viruses by constructing replication-competent virus-like particles either carrying fluorescent proteins or small luciferase, and such strategy requires people to reverse genetically modify each viral strain, which is usually time-consuming and challenging. A promising alternative is to try to harness the ability of RNA dependent RNA polymerase (RdRP), an essential protein encoded in the genomes of all RNA-containing viruses with no DNA stage, and build RdRP based synthetic circuits for detection and defense against positive sense single-stranded RNA viruses in vivo by introducing RNA parasites in host system to stall or stop viral replication. This additionally could potentially provide an alternate strategy, one that does not depend on host immune responses, for therapeutic host resistance against viral infection.
Why did you choose Caltech? "I chose Caltech because of its strong research atmosphere that fosters exploration, curiosity, and interdisciplinary collaboration in its tight knit community. Ever since my first visit here, Caltech has become the place where I am excited to build strong connections and find invaluable mentorship. I particularly look forward to indulging myself in the variety of opportunities presented at Caltech in hopes of reducing the gap between advanced technology and medical implementation in practice."
What are you most looking forward to as you participate in the BLP at Caltech? "Through involvement with BLP, I hope to gain perspective and appreciate the many facets of biotechnology that will help me understand the gap between academic research and pathways leading to commercialization and deployment of a product. Additionally, the internship opportunity uniquely provides an experience for me to immerse myself in an industrial research setting and to understand the complexities presented apart from scientific challenges which will also allow me to actively explore new ways in which I can contribute to helping others."
Advisor: Scott Cushing
Current Research: Quantum entangled photons enable classically impossible optical applications. They can be used to measure wavelengths inaccessible to commercial detectors. Ultrafast measurements also become possible with entangled photons generated from continuous wave (CW) laser diodes. Moreover, entangled photons linearize nonlinear optical interactions: a CW-pumped entangled photon source at nanowatt powers can rival a pulsed laser with megawatt peak powers in two-photon fluorescence imaging. In my lab, I develop low-cost, compact, and ultimately on-chip entangled photon sources that can transform medical imaging and laser therapies into truly portable and non-invasive techniques. The entangled photons used will also provide rich, nonclassical information that will help improve the accuracy and range of clinical optical diagnostics.
What about biotechnology excites you? "In recent years, biotechnology has been shifting towards portable, noninvasive, and digital solutions. I am excited that patients' comfort and quality of life are becoming an essential part of product design."
What is one thing we would be surprised to know about you? "I have been fencing saber as a hobby since the age of 14."
Advisor: Frances H. Arnold
Current Research: Engineered proteins have advanced industrial biocatalysis, medicine, therapeutics, and agriculture, bringing significant environmental benefits. Given the vastness of protein sequence space, the rarity of functionally enhanced variants, and the difficulty of developing protein functional assays, the need for robust, high-throughput screening methods is apparent. Machine learning (ML) can provide this. However, predicting protein multi-mutant function from single mutant data remains challenging due to the non-linearity of protein sequence-function relationships. To tackle this, Francesca has been compiling suitable datasets and testing different ML prediction strategies. For example, just as the meaning of a word changes depending on its context, the functionality of an amino acid depends on the context of the sequence in which it is found. Leveraging natural language processing tools and existing data, multi mutant fitness can be predicted from single mutant data and its performance is benchmarked against the baseline linear predictions.
What about biotechnology excites you? "Believing that true innovation happens when interdisciplinary science and engineering meet real-world challenges, I am excited by biotechnology as a rapidly growing field with the potential to transform society. Specifically, given the recent advancements in computation abilities and the expansion of big data, I am passionate about harnessing their power for biological engineering applications."
What are you most looking forward to as you participate in the BLP at Caltech? "Through the internship, I hope to gain relevant computational research expertise, engage in cross-department teamwork, experience different corporate cultures, and develop strong connections. Additionally, I am excited for events to explore different biotech career paths, advance management skills for leading not only talented, but also diverse, equitable, inclusive teams, and bonding with the inspiring BLP community and beyond."
Advisor: Mitchell Guttman
Current Research: Proteins are the workhorse of biological systems, yet targeting them for either discovery or therapeutics is much more challenging than targeting their nucleic acid counterparts. While more recent technologies have allowed DNA and RNA to be identified or manipulated at high-throughput levels, proteins are targeted selectively, with often only a few well characterized affinity reagents to target them with. The development of new protein affinity reagents such as antibodies is often expensive and time consuming, dependent on the inoculation of mammals against a specific antigen of interest. In the Guttman Lab, Linlin's goal is to build a platform to generate protein targeting reagents in a multiplexed, streamlined manner, using in vitro techniques that bypass the conventional use of mammals. Linlin received her undergraduate degree in Neuroscience from Wellesley College. Prior to attending Caltech, she spent two years at the Broad Institute developing a molecular tool for recording cellular activity over time.
Why did you choose Caltech? "Caltech is a place where people are passionate about the work they do. It's a small community that promotes amazing interdisciplinary collaboration and dynamic discussions about science and the world around us. I chose to come to Caltech to surround myself with the types of people I admire."
What about biotechnology excites you? "While advances in biological discovery change the knowledge we have about the world, advances in biotechnology change how we can interact with it. Building something new with the biological tools available to us can help solve high impact problems in health and sustainability, but also open new avenues to the types of questions we can ask in biological systems. The potential in biotechnology is unparalleled, and deeply exciting to me."