‘ve always wanted to deconstruct complex biological phenomenon into simple motifs – my interest in systems and networks start from high school, when I wrote a short thesis ‘Understanding of hubs using virus spreading model’ and was awarded Youth Scholars Award. My habit of making sense of the world by identifying parameters, simplifying interactions, and eventually modelling stayed with me. These habits developed from competing in Korea Youth Physicists Tournament, solving open-ended questions like ‘Explain how ancient Vikings navigated using polarizing materials’. In university, traditional reductionist approach in lectures, mainly based on mutation or knockout studies, didn’t satisfy my curiosity. During my undergraduate studies, I was thirsty about providing a framework that explains why cellular decisions occur the way they do.
Through iGEM, I modelled gene expression and diffusion of our antimicrobial proteins, and estimated the number of E. coli that would make our project a more effective treatment than antibiotics. Furthermore, I’ve taught myself how to model with 2×2 systems of differential equations. Following these experiences, I wanted to answer more fundamental questions such as how cells make decision in a noisedominatedsystem, or identifying genetic circuits that are behind temporal / spatial pattern formation. I learned that cells in the pathological state possess completely different set of gene expression, metabolism and dynamics of signalling pathways, during my internship in Botnar research centre.
I also hope to reveal critical differences of network dynamics between healthy and pathological cells, as well as evolution of network dynamics from healthy to pathological cells. Deconstructing a very complex biological network, such as limb development and pattern formation, into a simple motif will allow reconstruction of emergent properties. I am fascinated by networks because they allow to investigate the underlying principles of cellular decision-making, ranging from B.Subtilis competence to stem cell differentiation.
In the long run, I want to characterise dynamics of genetic networks in in vivo context, and to predict the behaviour of organisms. For instance, I would be excited to see how computational surveys on existing networks, such as Wnt and Sonic Hedgehog pathway, would reveal about their boundary / gradient formation mechanisms. Another example would be alteration of network dynamics by microfluidic device, and assaying cellular responses. My scientific interests are centred around questions such as : How can a noise in a complex biological network can be experimentally measured and modelled? How does change in dynamics of the network influence cell decision? How are networks rewired during evolution? I wish to devise novel, reliable approaches to answer these questions. These interests closely match with that of Prof. Levchenko’s group, especially bringing these above questions in the context of living cells.
For instance, reading “Limits to the precision of gradient sensing with spatial communication and temporal integration”, I have clarified my understanding of a in vivo cellular communication. I’ve learned that gradient sensing requires to communicate information from multiple detectors to a common location: I’ve previously came across it only in the context of adjacent cell communication in 1D row1. Single cell approach, which would further illustrate intrinsic variability of cell responses, is another reason I want to join the Levchenko lab. By analysing the noise properties of a specific network, I want to implicate topology and dynamics of the regulatory network. Using microfluidic devices to delicately control single cell environment, I want examine how cell-to-cell variability add up to overall decision making process.
If I have the opportunity to join the group, I wish to explore both wet-lab and dry-lab aspect of modelling, starting from altering network dynamics in a targeted manner with microfluidic devices, to integrating data into simulated models. “Design and characterisation of combined hierarchical post-transcriptional switches” aims at finer control of gene expression, instead of switch-like activation or repression. The design combines two different types of small RNA, which are respectively complementary to the translation initiation region(TIR) and terminator sequences of mRNA. I hypothesised that by identifying that sRNAs complementary to the TIR and Small Transcription Activating RNAs(STARs) complementary to the terminator sequences operate independently, in an orthogonal manner.
I designed constructs of different length of small RNAs, expressed sRNA containing plasmids in E.Coli, and successfully observed decreased expression of target protein. The project ultimately allows modulation of accurate gene expression in synthetic circuits. To achieve this, I designed 5 different sRNAs with different lengths and binding energies to TIR of the template mRNA. Identical approach will be applied to STAR system, and we hope to alter switch-like STAR system to stepwise activation.
Use of sRNA is a big leap from traditional methods such as random mutagenesis or selection from limited set of RBS / promoters.Undergraduate Projects (3 months each): My iGEM(international genetically Engineered Machine) project aimed at in-situ detection of pathogenic bacteria, followed by secretion of DNase, biofilm degrading protein, and artilysin, leading to specific eradication of pathogenic strains. During my internship at Botnar research centre, I came up with the new hypothesis that bromodomain inhibitors demonstrated notable decrease in Ewing sarcoma cell viability.
How PhD in Yale will help my future careerI aim to be a good bio-engineer, continuing to 1) investigate interdisciplinaryscientific questions / problems that interest me, and 2) utilizing adequate and ingenious methods to answer those questions. Whether it would be a startup, industry or academia, I want to tackle those questions in an environment with smart, passionate and dedicated people. Physical and Engineering Biology graduate programme would be the best experience I could gain at this stage, both in terms of broadening my scientific understanding and honing my skills as an bio-engineer. I am personally in favour of the 1) emphasis on dynamic systems of Yale PEB programme, which closely aligns with my current scientific interest explained above, 2) Combination of Hands-on, project based learning and lectures in the first/secondyear. Interdisciplinary knowledge and skills I would gain from PEB programme would ultimately help me to become an independent researcher with unique perspective.