Carter Laboratory
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Robot Team

The Robot Team or Mammoth Makers is a group of 6 students who come together over the summer for an 8 week program to build a robot. There is no programming, electronics, or robotics skills required. Everything is learn as you go. The team designs robots according the American Society of Mechanical Engineers (ASME) competition rules, but then uses these robots to teach inspire local middle schoolers. If you are interested in being a part of the Mammoth Makers then contact Professor Carter. Applications usually go out in March.

--2018 - Arnold the pentathlete and Eugene the soccer player (in honor of the 2018 FIFA World Cup)
--2019 - Arnold the pentathlete and Darlene the paper-tower-building robot

Undergraduate Research Projects

**The Carter laboratory is looking for undergraduate researchers (maybe you!) to work on a variety of projects in biophysics. We are especially interested in first year or sophomore students that can start over the summer or January term. Read below to see if any of our projects might interest you.

Molecules inside of the cell are not static. They bind, fold, unwind, cleave, and open in order to carry out cellular processes. We want to measure this motion and the forces that are involved to understand how chemical energy is used to do work. To this end, all of the projects focus on nanoscale mechanics and are a great blend of biology, chemistry, and physics. Thus, we look for a wide variety of undergraduates with different interests. Perhaps you are interested in the medical applications of this research in gene therapy or embryogenesis. Or maybe you are excited by the basic science of figuring out how the cell works. Or maybe you are interested in these projects from an engineering and materials stand point, since we are essentially studying an incredibly complex, active (living) material with interesting applications. Whatever your interests, you are sure to find these interdisciplinary projects exciting and challenging. No prior knowledge is required, just curiosity and hard work!

DNA Folding in Sperm
Specifically, we are interested in looking at the process of DNA compaction within the sperm nucleus. The DNA in each cell is about 2 m long and needs to be compacted ~1,000,000 times into a nuclues that is on the order of ~1 um. In sperm cells, this DNA compaction is incredibly important for making a hydrodynamic sperm head, with incorrect folding leading to infertility. The protein that folds DNA in sperm is the protamine protein. Protamines are small (50kDa) positively charged proteins that compact the DNA in a dramatic fashion. But, how does this compaction occur? What is the physical mechanism for protamine to compact the DNA? Thus, studying DNA folding by protamine will not only be important in fertility research, but also in biomaterials research where we want to be able to mimic this folding on engineered DNA strands. There the question will be: Can we repeat this mechanism with a similar molecule? Can we use protamine to fold DNA into an engineered macromolecular structure?

Undergraduates in the lab will use microscopy techniques to directly visualize DNA folding by protamine. This might include atomic force microscopes (AFMs) that image the DNA on a surface or tethered particle motion (TPM) assays that directly measure folding. In a TPM assay, we attach one end of the DNA to the surface and the other to a micron-sized bead. As the DNA condenses, the Brownian motion of the bead decreases, indicating the length and condensation of the DNA. However, to measure the energy landscape for this folding event we need to measure force on the order of a picoNewton and positions as small as a nanometer. Force and position at this scale can be measured with an optical tweezers system (Figure 1). In an optical tweezers system, a focused laser beam traps the bead in the focus of the laser. Movement of the laser focus then moves the bead, allowing us to apply force and making it look like the bead is being manipulated by a pair of tweezers. Measurements of DNA folding using these three types of experiments are already underway!

Students interested in this project will learn about optics, computer programming, single molecule biophysics, microscopy, and DNA folding. If you are looking to learn these skills, send me an email and we can schedule a time for me to show you around.

Figure 1:
Picture of the old optical tweezers system in Merrill 206 before moving it to Beneski 004. Here we have a home built microscope and a cast iron table that is a remnant of Bell labs (awesome). Our new digs in Beneski 004 have all new optics.

Histone Replacement
Another related project to DNA folding in sperm is to look at the pathway for how protamines replace the histone proteins that typically fold DNA. Depending on the organism, protamines will either directly replace these histone proteins, or protamine will replace an intermediate protein that replaces histones. Once the histones have been removed, protamine molecules coat the DNA, loop it into a toroid, and eventually form toroid stacks in the sperm nucleus. This process creates a compact sperm head, but has many unanswered questions. How does protamine replace histones? Do different protamines fold the DNA differently or play different roles in replacement? Answering these questions will give biomaterials insight into using protamine-DNA structures in nanoengineering, biophysical insight into polymer folding, and epigenetics insight into how DNA folded structures may be passed on to subsequent generations.

DNA Folding in Viruses (NEW in 2020)
With the outbreak of the coronavirus in Spring 2020 many people are starting to focus on SARS-CoV-2, the virus that causes the disease COVID-19. One of the questions that the Carter Lab is interested in is how nucleic acid (RNA, DNA) is packaged into a virus. This is an important question since interfering with this packaging process could be used in anti-virals.

To solve this question, we will be looking at the interactions between the nucleocapsid (N) protein from SARS-CoV and nucleic acid. We want to know if the N protein can fold double stranded DNA, in addition to RNA. And, does it use a similar pathway as protamine, the protein that we have studied extensively. If so, there might be some interesting basic physics that defines DNA compaction.

Mechanics of Cytoskeletal Formation
Cellular mechanical properties play an important role in cell shape, differentiation, adhesion, and growth. Many of the mechanical properties of the cell are determined by the cytoplasm, a complex heterogeneous material consisting of a viscous fluid and an elastic cytoskeleton. Our goal is to measure the mechanical properties of cytoskeletal formation. This is important in embryogenesis, stem cell research, biomaterials research, and biophysics.

The mechanical properties of the cytoplasm can be measured by tracking the Brownian motion of injected particles in a technique known as microrheology. In this technique, we use video microscopy to record the Brownian motion of a bead injected into the cytoplasm. This Brownian motion is dependent on temperature, particle size, and of course the mechanical properties of the cytoplasm. Thus, measuring the bead's movements give us insight into the mechanical properties of the cell. However, in order to get statistically significant measurements using microrheology, many particles (~50) must be tracked. So to measure cytoskeletal formation we need large cells so we can track many particles in different geographical regions. For this reason, we use the large (1-mm-diameter) single cell stage of the zebrafish embryo (Figure 2). Specifically, this novel approach allows us to measure the mechanical properties of the cell as the cytoskeleton forms.

Students working on this project will learn about zebrafish embryology, cellular rheology, computer programming, microscopy, zebrafish maintenance and breeding, microinjection, and particle tracking.

Figure 2:
Left. Picture of a Zebrafish embryo (total diameter is 1 mm). Center. Cells are shown at the right, while micron-sized beads float in the chorion layer (a layer of fluid in a sack surrounding the embryo). Right. The beads move randomly within the fluid, exhibiting Brownian motion. Tracking them allows us to measure viscosity.

The Modern Laboratory Blog

Somewhere in my first year as a professor I realized I was running my laboratory all wrong! The undergraduates couldn’t follow the chicken scratch in the lab notebook that detailed how to make samples, the external hard drives we were using to store data kept breaking, and preparation for lab meetings was taking over my student’s week. This is in addition to the normal woes of the ever increasing load of administrative tasks and teaching requirements. So to procrastinate, I started searching for a way to get things done faster, make things simpler, or do things better using technology. And to my surprise, solutions did exist. The Modern Laboratory is my “captain’s log” of those solutions in blog format. Of course, this is not a real blog since I only post things here when I get a chance. Also take a look at my editorial in AJP that details some of my fumbles and fixes.
The Modern Laboratory
AJP editorial on "Building a Lab, not starting one"

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