(6dc) Investigating Biophysical Interactions Using Coarse-Grained Simulations

My primary interests are in teaching and educational research, specifically implementing novel education methods in and out of the engineering classroom. I also have interests in computational biophysics that are especially well suited for undergraduate researchers.

Educational research: There are many educational methods that help students better comprehend classroom material in lieu of or in addition to traditional lectures, including approaches that can be broadly applied, such as flipping a classroom, to topic-specific methods, such as classroom demonstrations. However, implementation of even the simplest methods is sparse in engineering classes. I want to study the barriers to implementation of novel educational methods both in and out of the classroom. I also want to understand how those barriers might differ for instructors in different career paths (lecturer to tenure-track), those at different stages of their careers (new to established), and those at different college types (teaching-focused to R1 institutions). With this knowledge, I will develop feasible solutions to those challenges from the faculty to the administrative level.

Efficient simulations of the blood–brain barrier and DNA replication systems: Simulations of biophysical interactions can reveal fundamental information about biological systems that is challenging to obtain with experimental techniques. However, a typical atomistic (or near atomistic) simulation of a single biomolecule can take weeks of computational time. To study more complex or larger systems, one can coarse grain the system by systematically removing details that do not impact the large-scale behavior of interest. This not only leads to more computationally efficient simulations, but also allows for hypothesis and confirmation of the interactions that are critical to the experimentally observed behavior of interest. I will apply this method of coarse-graining to two specific systems: the blood–brain barrier and a transcription factor-polymerase-DNA system. While the critical interactions in each system will vary (such as relationship of time scales, electrostatics, repulsive and attractive forces), the same coarse-grained “toolbox” can be applied to any number of systems, which makes this research topic well suited for undergraduate work.

Research Background:

My postdoctoral work at Washington State University (WSU) with Prof. Bernie Van Wie is focused on the national dissemination and assessment of low-cost desktop learning modules (LC-DLMs) that were developed at WSU. The following modules are used in tandem with traditional lectures to help students visualize abstract concepts that they are learning in class:

• Venturi meter
• Hydraulic loss
• Double pipe heat exchanger
• Shell and tube heat exchanger

Prior work at WSU demonstrated that students’ understanding of concepts is improved when LC-DLMs are utilized, and we are implementing a systematic approach to spread the use of LC-DLMs to chemical engineering departments at forty-eight additional universities. We have developed online video demonstrations, assessments, and a webpage to minimize the barrier to LC-DLM implementation, and we are implementing a five-year “hub and spoke” workshop model to train instructors on best practices for use in the classroom. This dual use of technology and training will allow us to uniformly assess student performance across different institutions. We will refine implementation of LC-DLMs in the classroom to further enhance students’ understanding and comprehension of core engineering concepts. In addition, we are developing a method to quantify interactivity in the context of the ICAP framework (Interactive, Constructive, Active, and Passive) using DLMs as a scaffold.

• Reynolds, O. (co-presenter), Kaiphanliam, K.M., Khan, A.I., Pour, N.B., Dahlke, K. (co-presenter), Thiessen, D.B., Gartner, J.B., Adesope, O., Dutta, P., and Van Wie, B.J. “Nationwide Dissemination and Critical Assessment of Low-Cost Desktop Learning Modules for Engineering: A Systematic, Supported Approach.” 2019 ASEE Annual Conference, Tampa, FL.
• Upcoming LC-DLM implementation workshops: Campbell University (Buies Creek, NC, September 6, 2019) and University of Central Oklahoma (Edmond, OK, September 20, 2019)

My work at the University of Illinois at Urbana-Champaign (UIUC), under the guidance of Prof. Charles Sing, focused on how architectural proteins in prokaryotes, known as nucleoid associated proteins (NAPs), help organize and structure the DNA at long length scales. My dissertation research investigated how local interactions between NAPs and DNA impact the long time- and length-scale behavior of the system, which in turn impacts the phenomenological behavior of the nucleoid, and thus, the cell. We developed novel coarse-grained simulations to study a model NAP-DNA system, which incorporated critical local interactions, such as intermediate binding states that NAPs typically exhibit as well as physical deformations of DNA upon protein binding. We investigated the cooperative and competing behavior of NAP-DNA interactions that resulted in concentration-, force-, and topology-dependent changes to both protein kinetics and physical DNA behavior. Specifically, we discovered how different parameters in the system, namely the energy barriers separating the three possible protein states and force applied to DNA, affect concentration-dependent dissociation rates that had been experimentally observed. Additionally, we determined how DNA deformations caused by NAPs, namely local DNA bends, impact DNA elasticity and topology. These kinks in the backbone compact DNA and stabilize mesoscale structures such as DNA supercoils. Our model qualitatively matched experimental observations and provided a rigorous, physical explanation for the observed behavior based on cooperative local interactions.

• Dahlke, K., Sing, C.E. “Influence of nucleoid associated proteins on DNA supercoiling.”
• Dahlke, K., Zhao, J., Sing, C.E., Banigan, E.J. “Effects of force on facilitated protein dissociation: a new kind of catch bond.” In revision.
• Dahlke, K., Sing, C.E. “Force-Extension Behavior of DNA in the presence of DNA-Bending Nucleoid Associated Proteins.” 2018. J. Chem. Phys. 148, 084902.
• Dahlke, K., Sing, C.E. “Facilitated Dissociation of Dimeric Nucleoid-Associated Proteins Demonstrates Universal Behavior.” 2017. Biophys. J. 112, 543-551.

Teaching Interests:

My teaching philosophy centers on maintaining a classroom that is societally relevant and helping students integrate their external experiences with in-class content. I want students to understand and appreciate that what they are learning is broadly important; course content has applications beyond the classroom and even beyond chemical engineering. I will tie in contemporary societal examples, such as safety-related incidents or products that required non-obvious chemical engineering design. Students will be encouraged to actively think about how they might encounter course concepts in everyday life. I will also make thoughtful choices about what I expect from students both in and out of the classroom. For example, I will implement novel approaches to enhance learning, including:

• alternative ways to test student understanding, such as final projects and test-retake opportunities
• activities to drive interpersonal interactions, such as in-class problems and flipped lessons
• assignments to help students gain deeper or expertise-level knowledge, such as literature reviews and attending scientific seminars

I will also work to coordinate homework deadlines and exams across faculty in the department to ensure that students are not needlessly overwhelmed.

With a strong background in chemical engineering, I am enthusiastic to teach any core chemical engineering classes, including mass and energy balances, thermodynamics, fluid mechanics, transport phenomena, separations, kinetics, process dynamics and controls, and unit operations. I would also enjoy opportunities to develop topical electives based on my research background in polymer science or biophysics. Additionally, I have a strong interest in developing and teaching a computational course that goes beyond numerical methods and provides basic programming skills that can be widely applied. This skillset will be invaluable to undergraduate students, regardless of career path.

Teaching Experience:

• Biochemical Engineering (WSU ChE 475), Instructor (2019)
• Mass Transfer Operations (UIUC ChBE 422), Teaching Assistant and Guest Lecturer (2018*)
• SMArt (Science, Math and Art) outreach program (Urbana Middle School, Illinois), Lead Instructor and Curriculum Developer (2018)
• Thermodynamics (UIUC ChBE 321), Teaching Assistant (2017*) and Guest Lecturer (2018)
• Chemical Engineering Problems with Computer Applications Laboratory (Iowa State University, ChE 160), Teaching Assistant (2013)

*List of teachers ranked as excellent at UIUC