Home workspace tour: Ariane Nazemi

Electrical engineering undergraduate student Ariane Nazemi is a maker at heart. He enjoys designing, printing and painting miniature models; dabbles in printed circuit board modeling; and he even makes his own mechanical keyboards! 

As a student supervisor in the Electrical and Computer Engineering Makerspace, Nazemi had access to all the space and tools needed for these hobbies-- from 3D printers to laser cutters, soldering irons, and more. With the closure of this workspace and many campus spaces due to the COVID-19 pandemic, Nazemi decided to rearrange and spruce up his home work area.

Here's a tour of his space, featuring some of his creations. 

Digitizing the genome

by Cam Lamoureux, UC San Diego bioengineering PhD candidate 

The genome has historically been known as life’s instruction manual. Indeed, the genome sequence of any organism contains all of the information needed to specify its form and function, from the simplest single-celled bacterium to complex organisms such as humans. But with rapidly developing sequencing technology, the genome is taking the stage as a new type of hard drive, nature’s way of storing information.

Understanding exactly how the genome represents an organism’s information remains a challenge for scientists. Any given DNA base (A, T, C or G) in the genome sequence can be involved in multiple different functions. As part of a gene, for example, a DNA base codes for a particular building block, known as an amino acid, of the protein that the gene specifies. That amino acid, in turn, may be part of a particular shape in the final protein. The DNA base may also be part of a sequence on the opposite side of the DNA double helix that is involved in controlling another gene’s activity. With so many different functions, information encoded by the genome sequence is convoluted and overlapping, yet it is critical to understanding an organism’s behavior.

Our work in bioengineering professor Bernhard Palsson’s Systems Biology Research Group at UC San Diego addresses this challenge. We introduce a completely new way of representing this information. For every DNA base, we can answer a simple yes/no question about every type of information the sequence can encode: does this DNA base encode that information? Borrowing from computer science, we realized that the answer to this question can be thought of as a “bit,” a binary digit. By doing so, we can scan across the entire genome of any organism, ask this question, and tabulate the answer as 1 for “yes” and 0 for “no.”

With this approach, we can construct a clean, quantitative record of the bits of information that an entire genome encodes. We call this method of genome annotation the “Bitome.”

We envision that the Bitome will serve as a key foundational tool for genome engineering, with applications in the sustainable production of industrial and medical compounds. For example, bioprocess engineers who reprogram bacterial genomes to sustainably produce chemical compounds can use our method to quickly assess which parts of an organism’s genome sequence are important for their application, and which are less important. They can make predictions about how proposed changes to the genome sequence will affect the organism.

While the Bitome’s capability mirrors traditional genome browsers, our approach provides far more utility and flexibility. Because we have digitized genome information, we can perform computations on those bits of information.

As a test case, we studied the E. coli genome and showed that DNA bases that contain fewer bits of information are more likely to be mutated during adaptive evolution. Because this observation is based on information that can be encoded by any genome sequence—not just E. coli—it could be used to predict genes that are more likely to mutate in cancerous tissues, for example.

The Bitome’s digitized representation facilitates prediction with machine learning. In part of our study, we applied machine learning to pinpoint the use of a particular stop codon as a predictor of mutability. This result is significant because it provides a deeper understanding of how genes mutated during adaptive evolution, a key tool for genome engineering. We also used machine learning to predict gene essentiality directly from the genome, another key capability for engineering genomes.

We are excited by the potential future applications of the Bitome as a way of analyzing genome sequences. This concept is inherently extensible to any organism’s genome and will undoubtedly serve useful both for deeply understanding the information encoded in a genome and for predicting behavior based on that information. With this work, we hope to further bridge the gap between the genome sequence information and the complex, critical functions that it encodes.

Publication: Lamoureux, C. et al (2020) The Bitome: digitized genomic features reveal fundamental genome organization. Nucleic Acids Res. https://doi.org/10.1093/nar/gkaa774

Summer 2020: a virtual NASA internship

The summer of 2020 was a far-out one for many people, but for Ferrill Rushton, a 2020 electrical engineering alumnus of the Jacobs School, it was really, really far-out; to deep space, to be exact. Rushton, who is returning to UC San Diego this fall to work towards his master’s degree in photonics, was an intern at NASA’s Space Communication and Navigation (SCaN) Internship Project, analyzing photon counting methods that affect deep space communications.

The internship was designed to be an in-person research experience, but Rushton and the NASA team quickly transitioned to create a meaningful remote internship when the COVID-19 pandemic forced many plans to change.

Rushton's at-home setup for his remote
NASA internship

When electromagnetic radiation from certain deep space communications or low-power systems in low-Earth orbit gets to a receiver on Earth, there is so little incoming light that the photons actually need to be counted. Rushton’s job this summer was to quantify the inefficiency in photon counting methods in situations where a ground station is detecting incoming light from these photon-depraved situations. The results from his project—Finding the Modes of Arbitrary 2D Geometries Using Finite Difference Techniques—will be incorporated into existing NASA frameworks.

“I don’t feel like I was given work just so there could be an internship, they had all this real work for us,” Rushton said.

The internship allows students to perform hands-on training with real mission scenarios, gain exposure and analyze powerful space communication systems, utilize networks software tools and effectively communicate their findings in a final presentation to NASA management. Each student is paired with an experienced and multidisciplinary mentor who counsels the student with his/her work, and also engages with career planning.

Rushton speaking with former NASA astronaut
Alvin Drew during his virtual 2020 NASA internship. 

At UC San Diego, Rushton was involved with SPIE—the International Society of Optics and Photonics—serving as treasurer of the UC San Diego branch last year. He is also involved in Engineers for Exploration, on the Maya Archaeology team.

His advice to current and future students?

“If there's something that you want, there's no reason not to apply for it. Never be afraid to put yourself out there.”

Evolutionary assimilation of foreign DNA in a new host

 

We know from decades of biological study that all living beings share many similar genes. We also know that these genes are subject to evolution, from mutations that change the DNA sequence of an organism’s offspring, or through horizontal gene transfer (HGT), the acquisition of DNA from a creature other than a parent, and even of a different species.

This got a team of bioengineers at UC San Diego wondering: could a human gene function in other organisms? And if it does function, what evolutionary changes are happening to the DNA to allow it to work properly in a new host species?

Bioengineers in Professor Bernhard Palsson’s Systems BiologyResearch Group used genetic engineering and laboratory evolution to test the functionality of DNA placed into a new species and study how it can mutate to become functional if given sufficient evolutionary time. They published their results on August 10 in Nature Ecology and Evolution.

Schematic of the experimental workflow. Native E. coli glycolytic isomerases pgi and tpiA were replaced with the coding sequence of foreign orthologues and subjected to laboratory evolution for improved exponential phase growth rate. Ma, million years ago.

The researchers used the bacteria E.coli to answer these questions. They took two common genes from the human genome involved in sugar metabolism, and used CRISPR to swap them into a commonly used laboratory strain of E. coli.

The two genes used—pgi and tpiA-- cripple E. coli when removed, causing the bacteria to grow about 5 times slower. Initially, following the gene swap, E. coli’s growth rate did drop, signaling that the genes weren’t functioning properly. But then, the researchers subjected the transformed E. coli strain to a laboratory “evolution machine”—a robotic system used to study how engineered bacteria adapt to changes. After thousands of generations of evolution, the new genes started to function properly. The human genes could serve just the same function in the bacterium as its own genes.

The automated evolution system enabled a large-scale study, generating hundreds of mutant strains evolved for more than 50,000 cumulative generations, something that would take decades rather than months if performed manually.

How was it possible that the human genes were fulfilling the same role in E.coli?  The researchers sequenced the genomes of the evolved strains to find out.

For every strain that successfully evolved, the critical factor was one or more mutations increasing gene expression level. Most of these mutations did not occur within the foreign gene, but rather in regions of E. coli’s DNA controlling regulation of the gene, with their nature depending sensitively on the gene’s specific DNA sequence and location in the chromosome. Some of these mutations occurred with shocking regularity, including one observed independently more than 20 times, demonstrating that evolutionary outcomes can be (probabilistically) predicted to the single DNA basepair.

“This result shows the importance of systems biology,” said Professor Bernhard Palsson, principal investigator of the study. “Namely, biological function, in this case, is not so much about the parts of the cell, but how they come together to function as a system.”

The original motivation for the study was to determine ’self’ versus ’non-self’ at the molecular biology level. The surprising answer is that even if human enzymes are foreign entities to the E. coli bacterium, they are not recognized as such, and the bacterium adopts their function by simply adjusting their abundance to achieve balanced phenotypic state.

This study establishes the influence of various DNA and protein features on cross-species genetic interchangeability and evolutionary outcomes, with implications for both natural horizontal gene transfer and strain design via genetic engineering.

NanoEngineer earns Dissertation Year Fellowship

Jacobs School of Engineering nanoengineering PhD student Qiaowan Chang has been awarded a Dissertation Year Fellowship funded by the Marye Anne Fox Endowed Fellowship Fund. This fellowship is awarded to students who demonstrate highly distinguished academic records, and provides recipients with a $22,000 stipend for their dissertation year, plus tuition and fees.

Qiaowan Chang

We spoke with Chang about her research, her accomplishments at UC San Diego, and her future goals.

Q: How did it feel to receive this award?

A: I feel very excited and lucky to receive this award. It's not only a recognition of my current research, but also encouragement for my future work. And thanks to my supervisor, Professor Zheng Chen, for the instruction, the help during my PhD studies, and for offering lots of opportunities to collaborate with other groups.

Q: Tell us about the research you’ve been conducting in Professor Zheng Chen's lab.

A: My research is mainly focused on designing electrocatalysts at atomic scale through fundamental understanding of their elementary processes in several key electrocatalytic applications and reactions, including decentralized hydrogen peroxide (H2O2) production (2-electron oxygen reduction reaction), direct liquid fuel cells (ethanol oxidation reaction), and carbon dioxide (CO2) conversion (carbon dioxide reduction reaction).

Q:  What are some of the applications of your research?

A: For the decentralized hydrogen peroxide (H2O2) production (2-electron oxygen reduction reaction), H2O2 is one of the most useful chemicals across the entire chemical industry. For the traditional production method, the transportation and storage of H2O2 are unresolved problems due to its chemical instability. Only a dilute H2O2 solution is needed for most applications. For example, 3% H2O2 solution is used as the disinfectant to fight the COVID-19 virus. My research is to develop a green and user-friendly method to produce H2O2 on-site from the two-electron oxygen reduction reaction.

For the direct ethanol fuel cells (ethanol oxidation reaction), it could be used in electric vehicles. In direct ethanol fuel cells, ethanol is oxidized by oxygen to generate electricity. Ethanol is a green and sustainable fuel that can be produced from agriculture feedstocks. Thus, direct ethanol fuel cells are environmentally-friendly techniques for powering vehicles.

For the carbon dioxide (CO2) conversion (carbon dioxide reduction reaction), electrochemical technology could reutilize and convert CO2 to other important chemicals to mitigate climate change and ocean acidification caused by the increased CO2 level. 

Q: Tell us about your dissertation topic.

A: My dissertation topic is to explore novel strategies to design electrocatalysts at atomic scale through fundamental understanding of their elementary processes in the above applications and reactions. The key to make such electrochemical reactions happen is the electrocatalysts. The thesis mainly discusses several strategies, including to tune the local chemical coordination between atomic catalyst clusters (metal) and their support materials (defect carbons) using a composite approach to achieve the synergistic effect of “1+1>2” (that is, Pd clusters deposited on the oxidized carbon nanotubes) for decentralized hydrogen peroxide (H2O2) production (2-electron oxygen reduction reaction), and to control the morphology and structure of the electrocatalyst (that is, the core-shell cubic-shaped electrocatalysts: 10 nm of platinum (Pt) nanocubes as a core and a ~0.2 nm thick of iridium (Ir) layer as a shell) in direct ethanol fuel cells (DEFCs).

Q: What are your future goals once you earn your PhD?

A: I will do a postdoc first to finish my remaining projects. Then, I will try to pursue a faculty position in academia, or a researcher/scientist position in industry.

Using nanotechnology for more targeted, safer pesticide delivery

Nanoengineers at UC San Diego will develop more targeted ways to apply pesticides to food crops using plant virus nanocarriers, thanks to a $490,000 grant from the Department of Agriculture’s National Institute of Food and Agriculture. This could lead to a reduction in the amount of pesticide used, and therefore less chemical accumulation from pesticides in our food, drinking water and environment.

Engineers are using a plant virus as a nanocarrier
for more targeted pesticide delivery to protect crops
like tomatoes from root-eating nematodes. 

Pesticides are used extensively in food production to ensure crop health and yield. While these toxic chemicals can keep bugs, weeds, parasites, fungi and rodents from damaging crops, they also accumulate in the environment, in the crops themselves, and even in drinking water supplies, leading to adverse health effects for humans.

Nanoengineers led by Professor Nicole Steinmetz at the Jacobs School of Engineering plan to use a plant virus as a nanocarrier to more precisely deliver pesticide payloads when and where needed, resulting in less pesticide required, and less bioaccumulation. The team will study and use the tobacco mild green mosaic virus (TMGMV), which they’ve previously shown can carry cargo down to 30 centimeters below the soil surface, much deeper than traditional synthetic nanoparticles which travel 8 to 12 centimeters deep.

Their first target for these nanoparticles is a type of roundworm called a nematode, which eats plant roots, destroying the plant in the process. By being able to deliver the pesticide deeper into the plant’s root system, the researchers believe their plant virus nanoparticles will be more effective in stopping nematodes than synthetic pesticide delivery particles.

“In this project we focus on pesticides to target roundworms that infect the roots of crops, using our plant virus nanotechnology,” said Steinmetz.  “More specifically we will produce a library of nanoparticles derived from harmless plant viruses to answer how size, shape, and materials properties affect the nanocarriers interactions with soil and plants. Understanding these fundamental questions is expected to make an impact on next-generation pesticides, literally attacking the problem at its roots.”

Since plant viruses like TMGMV can be engineered to a custom size and certain physical properties, the researchers will study the effectiveness of plant virus nanocarriers of different sizes, shapes, and surface chemistries.  They’ll create a library of nanomaterials derived from TMGMV, detailing the nanocarriers’ pesticide delivery efficacy.

“We’ve seen that in medicine, changing the shape of a nanoparticle delivering a specific drug can lead to advantages such as enhanced diffusion and tissue penetration,” Steinmetz said. “We hypothesize that this is true for pesticide delivery as well, and will investigate the effect of nanocarrier size and shape on pesticide application effectiveness.”

The tobacco mild green mosaic virus is non-infectious to most plants, but the researchers will also create inactivation protocols to ensure it’s safe to use with any desired plant.  The virus is non-infectious in humans.

Steinmetz will collaborate with researchers Erin Rosskopf and Jason Hong at the USDA Agricultural Research Service, who will test candidate materials on nematode-infested crops.

Comic-Con@Home features UC San Diego scientists

Saura Naderi, outreach director at the Halıcıoğlu Data
Science Institute

Comic-Con 2020 may look a little different this year, coming to you from the comfort of your own home. The annual San Diego comic and pop culture convention is going virtual due to COVID-19, but the good news is more than 350 panels will be available for free online, no waiting overnight in line required.

Comic-Con@Home will feature seven UC San Diego speakers during the five-day virtual event running from July 22 to July 26.

Tune in on Thursday, July 23 from 3-4pm for The Science of Back to the Future, where the creative teams from "Back to the Future" and "Transformers" talk to local scientists about how they came up with their vision for each storyline and how science would play a part in these movies. UC San Diego panelists include engineer and roboticist Saura Naderi, the outreach director at the Halıcıoğlu Data Science Institute and an alumna of the Jacobs School of Engineering.

Marine biologist Ben Frable will speak on
the More Science in Your Fiction panel.

Up next is The League of Extraordinary Scientists and Engineers: More Science in Your Fiction on Thursday, July 23 from 6-7pm. Scientists and engineers will discuss how both comic books and science fiction push them to dive deeper into the unknown. UC San Diego panelists include Ben Frable, a marine biologist at Scripps Institution of Oceanography, and Angela Zoumplis, an extremophile explorer at Scripps Institution of Oceanography.

You can catch Sinless, Fearless, Ruthless - A look at science and social science in a YA sci-fi book Friday, July 25 at 4pm. Learn about the social sciences and the idea of morality behind Eye of the Beholder by author Sarah Tarkoff. UC San Diego panelists include Samantha Russman, a PhD student at the Jacobs School of Engineering.

Cognitive Science Professor Virgina De Sa

The Fleet Science Center Celebrates: Agents of S.H.I.E.L.D. - The Stories and Science of Androids, Space Travel and Aliens will air on Saturday, July 25 from 3-4pm. Celebrate the seven seasons of Marvel's Agents of S.H.I.E.L.D. and hear executive producers, actors, and writers discuss how accurate the science in the series was with local scientists. UC San Diego panelists include Virginia De Sa, a professor in the Cognitive Science Department and associate director of the Halıcıoğlu Data Science Institute ; Troy Sandberg, a bioengineering PhD alumnus; and Melissa Miller, a scientist and science writer at the Scripps Institution of Oceanography. 

To learn more about Comic-Con 2020 events, visit their website.