Meet Ophelia Venturelli, Winner of the 2023 ACS Synthetic Biology Young Innovator Award

ACS Synthetic Biology, in partnership with The American Institute of Chemical Engineers, is proud to announce the winner of the 2023 ACS Synthetic Biology Young Innovator Award:

Ophelia Venturelli, University of Wisconsin-Madison, USA

This award recognizes an outstanding early career investigator conducting research in any area of synthetic biology. Professor Venturelli is being recognized for her pioneering and interdisciplinary research toward programming the spatiotemporal behaviors of microbiomes. In addition to addressing grand scientific challenges facing human society in human health, environment, and agriculture, she is committed to open science as well as fostering a more diverse and supportive community.

Professor Venturelli will be honored during the 2023 Synthetic Biology: Engineering, Evolution & Design (SEED) meeting on May 30 – June 2, 2023, in Los Angeles, Calif. Learn more about Prof. Venturelli and her research below.

Prof. Venturelli is an Assistant Professor in Biochemistry, Chemical & Biological Engineering, Biochemistry and Biomedical Engineering at the University of Wisconsin-Madison. The Venturelli Lab focuses on understanding and engineering microbiomes using systems and synthetic biology to address grand challenges facing society in human health, agriculture, and bioprocessing. The lab combines high-throughput experiments and computational modeling to predict, design and control microbiome functions across space and time. Prof. Venturelli began her appointment in 2016 after completing a Life Sciences Research Foundation Fellowship at the University of California - Berkeley in the laboratory of Dr. Adam P. Arkin. She received her Ph.D. in Biochemistry and Biophysics in 2013 from Caltech with Richard M. Murray (co-advised by Hana El-Samad at UCSF), where she studied single-cell decision making and fitness, and the role of feedback loops in a metabolic gene regulatory network.

Prof. Venturelli has received numerous awards for her cross-disciplinary research, including the Shaw Scientist Award (2017), Army Research Office Young Investigator Award (2017), NIH Outstanding Investigator Award (2017), and Wisconsin Alumni Research Foundation Innovation Award (2019).

Read the Interview with Prof. Venturelli

What does this award mean to you?

I am thrilled and honored to receive this award because I greatly admire the previous winners of this award and I have a deep passion for synthetic biology. I am happy that our work in engineering multi-cellular is highlighted by this award as an exciting frontier of synthetic biology. Our lab studies microbiomes, which are networks of diverse microorganisms that are ubiquitous on Earth. Engineering these systems holds tremendous promise for addressing grand challenges facing human society in agriculture, health, and sustainability. For example, communities could be engineered for environmental cleanup, to enhance plant growth and reduce our dependency on fertilizers or to deliver drugs on demand for next-generation precision medicine. Over the last two decades, researchers in synthetic biology have substantially advanced the ability to program the behavior of single organisms. However, single strains have limited intracellular resources. As a consequence, introducing synthetic circuits into cells can lead to unpredictable behaviors and negative impacts on host cell fitness due to couplings between the host-cell genome and the synthetic circuits. We can learn from evolutionary design principles that bacterial “superorganisms” do not exist, but instead, functions are partitioned among different interacting populations that coexist together in microbiomes. While programming the behaviors of multi-cellular systems has certain advantages, engineering these systems also presents challenges in maintaining stable coexistence between constituent community members and developing the capability to predict and design their temporal and spatial behaviors.

How would you describe your research to someone outside your field?

While bacteria are tiny and not visible to our eye, their impacts on the environment they inhabit are disproportionate to their size. Bacteria are the most abundant and metabolically diverse group of organisms on Earth. Bacteria do not exist in isolation but are embedded in communities, where they compete for limited nutrients and space. In addition, bacteria can help each other by releasing compounds to promote the growth of other bacteria or by removing toxins in the environment. The critical functions that they perform are distributed across constituent community members that coexist over time. For example, the microbial community inhabiting our gastrointestinal tract has co-evolved with us to break down the food we eat and provide key nutrients and produce molecules that influence our behavior. However, when this community is disrupted, the balance of different community members is altered, which in turn can have negative impacts on our health. While most cells in our body can be difficult to change, we could selectively introduce beneficial or remove harmful bacteria in our guts or introduce novel pathways to treat diseases or enhance human performance. To achieve these goals, we need to develop the capability to predict the dynamics and functions of this system and elucidate molecular and ecological control knobs to steer the system to desired states. Our lab aims to develop the tools and frameworks to control and design microbiome functions to our benefit. Major goals include engineering of the gut microbiome to selectively inhibit gut pathogens and manipulate key microbial metabolites that influence neurological activities and metabolic diseases. In addition, we have recently started to investigate plant-associated microbiomes to enhance plant growth, and we are designing microbiomes to transform waste streams into valuable industrial compounds for sustainability applications.

What do you think is the biggest challenge currently in your area of research?

We’ve had success in predicting the dynamic behaviors of microbiomes at an ecological scale. A key challenge is developing predictive computational modeling frameworks that can capture the system across multiple scales (e.g. transcriptome, proteome, metabolome, and ecosystem). These frameworks could be useful for identifying novel control knobs and designing interventions that alter multiple key system outputs simultaneously. There are a large number of species/strains and abiotic factors, and these variables can vary substantially across different environments (e.g. inter-individual variability in the gut microbiome). A major challenge is to develop ex vivo platforms that capture key physiologically relevant parameters and also enable high-throughput measurements to probe the different modes of the system. Our ultimate goal is to deploy our model-designed microbiome interventions to have a beneficial impact on natural environments. Therefore, a key challenge for these interventions is achieving robustness to variability and understanding the degree of “personalization” needed to yield a beneficial target function.

What is next in your research?

For the past 6 years, we have primarily focused on quantitatively analyzing and predicting the behaviors of microbiomes in vitro. We are excited to translate our model-designed microbiome interventions to control host phenotypes. Over the next 5 years, we hope to translate our microbiome interventions to the clinic and potentially to the field for agricultural applications. Towards these goals, we are developing high-throughput ex-vivo platforms systems to quantitatively analyze and predict the interplay of host-microbe, microbe-microbe, and microbe-environment interactions shaping microbiome behaviors. We also aim to develop novel computational models that combine physics and machine learning to balance model interpretability and flexibility for designing, quantitatively analyzing and predicting microbiomes across space and time. Finally, we are excited to engineer living bacteria to sense key environmental stimuli and dynamically control novel pathways to impact the environment. These engineered bacteria will be embedded into designed microbiomes to provide real-time information about key environmental states and perform specific functions to further enhance the beneficial properties of the designed microbiomes. Finally, certain environments have a high degree of spatial heterogeneity. Therefore, we aim to understand and engineer microbiome functions in spatially structured environments and potentially exploit these spatial parameters for control of system behaviors.

Have there been any highlights in your career to date that you are especially proud of?

I am very proud when trainees win research fellowships, and awards and eventually find jobs that are fulfilling and that they love after they move on from the lab. I am also proud of establishing a highly diverse and collaborative lab. Diversity in our lab is at multiple levels: members come from six different countries and have backgrounds spanning bioengineering, chemical & biological engineering, mechanical engineering, biology, and chemistry. I believe that this diversity of perspectives promotes creativity and is critical for tackling the complex biological problems that we work on.

What would your advice be to someone just starting out in the field?

Microbiomes are incredibly complex, and their quantitative contribution to the environment is largely unknown. I would encourage someone starting out in the microbiome engineering field to embrace the complexity of these systems. In addition, due to a large number of interacting biotic and abiotic factors, I believe that computational modeling and quantitative reasoning at the systems-level is critical for understanding and predictably engineering their behaviors. Microbiomes are multi-scale systems and have complex interactions with their hosts. Since there are so many techniques needed to probe microbiomes and the effects they have on the environment in a detailed and quantitative way, collaborations between groups that specialize in different techniques can be powerful.