Jonathan J. (Joff) Silberg, Ph.D. - US grants

This award, made to Rice University by the NSF Divisions of Biological Infrastructure (DBI) and Chemistry (CHE), in the Directorates for Biological Sciences (BIO) and Mathematical and Physical Sciences (MPS), respectively, will provide research training for 10 weeks for 10 students, during the summers 2010-2012. The focus of the program is biological networks -- the complex interactions among biomolecules that give rise to the diverse biological phenotypes observed in nature. The goal is to provide students first hand experience with cutting-edge interdisciplinary research that is needed to predict biological functions sufficiently in order to reprogram cells to avoid diseases or to perform new tasks. In the REU program, students will work on research projects under faculty mentors that draw from a range of approaches (classical biochemical and genetic to theoretical models that require computation) to study naturally-occurring genetic networks, artificial genetic and metabolic networks, and biomolecular structure, function, and evolution. This program will also provide: a creative opportunity for students to develop innovative biotechnological ideas; leadership development; seminars and career development workshops; stipend and travel support; on-campus housing; a capstone research poster symposium; and an ethics and responsible conduct of research discussion seminar. Students will be recruited nationwide, with particular emphasis on recruiting women and under-represented minorities, and selection of students will be done based on the faculty steering committee's evaluation of each applicant's transcript, personal statement regarding their interest and motivation for research, and recommendation letters. Assessment of this program is done via pre- and post-questionnaires as well by using the NSF-supported common assessment tool. More information on this program can be obtained online at https://ibb.rice.edu/ or by contacting Dr. George Bennett (Principal Investigator) or Lisa Blinn (Program Coordinator) at 713-348-4671 or lisa.s.blinn@rice.edu.

Intellectual Merit
In order to better understand which atoms in a protein contribute decisively to the key properties that support enzyme function, this project will generate libraries of natural proteins that contain different classes of mutations (random substitutions, glycine substitutions, backbone fission, circular permutation, insertions, and deletions) and examine how each mutation type affects protein folding and function within cells. Adenylate kinases will be used for these studies, since an abundance of pre-existing biophysical data can be tapped to interpret results from systematic mutagenesis experiments. This research will establish if the pattern of a protein's functional tolerance to different classes of mutation contains information on how different native positions within its primary sequence contribute to structure, stability, folding, dynamics, and function. This experimental strategy will be potentially useful for studying any protein for which an in vivo screen is available, including poorly behaved proteins that cannot readily be examined by in vitro physical methods.

Broader Impact
This broader impact of this project will be to provide training for graduate and undergraduate students interested in science careers. The PI and graduate students performing this research will conduct annual round table discussions for undergraduates enrolled at a nearby community college. These community college students begin their education in lecture courses and are not necessarily exposed to an environment that mirrors a research lab. Round table discussions will be used to increase student self-confidence by showing beginning college students that they can read a peer-reviewed research article, demonstrate to these students the benefits of research training, and facilitate community college student recruitment to research experiences. These efforts will vertically integrate undergraduate and graduate education by providing beneficial training for graduate students, building self-sustaining outreach from a research university to a minority serving community college, and offering research experiences for community college students.

This REU Site award to Rice University, located in Houston, TX, will support the training of ten students for ten weeks during the summers of 2016-2018. This REU site seeks to expose students to the excitement of biological research and the increasing contributions that different science, technology, engineering, and math (STEM) disciplines are making towards a detailed understanding of biological systems. To achieve this, students will work in labs that draw from an array of approaches - from classical biochemical and genetic to non-trivial theoretical modeling that requires computation. The research areas include: (i) biomolecular structure, function, and evolution, (ii) naturally-occurring genetic networks, (iii) synthetic genetic and metabolic networks, and (iv) ecological networks. The participating faculty mentors come from a range of departments including Biosciences, Bioengineering, Chemical & Biomolecular Engineering, Chemistry, and Computer Science. In addition to research, students will participate in workshops that focus on ethics and responsible conduct of research, professional communication, career opportunities, and the graduate school application process. In addition to presenting their research at a capstone poster symposium, students will be provided a creative opportunity to develop innovative biotechnology proposal ideas by working in collaborative groups.

It is anticipated that a total of 30 students, primarily from schools with limited research opportunities, will be trained in the program. Students will be recruited nationwide, with an emphasis on students enrolled at proximal minority-serving institutions, including community colleges and four-year institutions. Students will learn how research is conducted, and many will present the results of their work at scientific conferences.

A common web-based assessment tool used by all REU programs funded by the Division of Biological Infrastructure (Directorate for Biological Sciences) will be used to determine the effectiveness of the training program. Students will be tracked after the program in order to determine student career paths. Students will be asked to respond to an automatic email sent via the NSF reporting system. More information about the program is available at http://ibb.rice.edu/Content.aspx?id=563, or by contacting the PI (Dr. Joff Silberg at joff@rice.edu) or the co-PI (Dr. George Bennett at gbennett@rice.edu).

To better understand how the brain functions, scientists are in search of new methods to activate specific neurons in laboratory animals without restricting their behaviors. This research effort will create technologies that rely on magnetic fields to stimulate specific, genetically modified neurons. A major advantage of this "magnetogenetic" technology is fact that magnetic fields easily penetrate bone, skin and tissue making it easier for scientists to probe the role of specific cells deep within the body without using any implanted devices that could otherwise interfere with normal animal behavior or cause damage to the target tissue. Better understanding of how the brain works in laboratory animals will help reveal fundamental principles of computation in the brain that may apply across animal species to include humans. This deeper understanding of the brain is key for developing better diagnosis and treatments for neural disorders and to improve artificial systems like neural networks designed to operate like the human brain.

This work will focus on understanding how biogenic magnetic nanoparticles tethered to temperature sensitive ion channels render specific cells sensitive to magnetic fields. The major goals of this effort will be the development of a comprehensive theory for the mechanism of action for these magnetogenetic channels, and the creation of a set of transgenic fly lines that display robust behavioral responses to magnetic fields. These magnetogenetic fly lines will be compatible with Gal4/UAS system such that magnetogenetic channels can be easily targeted to specific cells. The outcome of this work will be both a fundamental understanding of magnetogenetic mechanisms and a set of transgenic fly strains that will empower researchers to probe neural circuits in this common model organism.

A major challenge to combating the global health crisis of antibacterial resistance is that antibiotic resistance genes (ARGs) can be shared among bacteria through a process called horizontal gene transfer (HGT). ARGs are present in wastewater, and there is little understanding of ARG health impacts potentially conveyed by recycling wastewater. Little is known regarding the conditions that result in HGT of ARGs from environmental bacteria such as those used to treat wastewater and pathogenic bacteria found in clinical infections. The goals of this project are to decipher how pathogens acquire ARGs from environmental bacteria present in water and wastewater systems and to understand how ARGs are propagated in water and wastewater microbial communities. This research will develop biosensors to monitor HGT of ARGs to understand how simple operational parameters in a wastewater treatment plant impact the reduction or proliferation of ARGs. If successful, the results of this project will identify methods of antibiotic resistance transfer in the environment and identify ways to halt this transfer during water treatment processes, protecting public health and the Nation's water supply.

Understanding the controls over horizontal gene transfer (HGT) in microbial communities found in the environment would impart an unprecedented ability to manage the growing threat of antibiotic resistance. While a variety of technologies are available for obtaining static snapshots of bacteria that have acquired antibiotic resistance genes (ARGs) through HGT, these existing approaches do not provide dynamic information on the pathways and rates of gene flow within complex communities that experience a changing environment. These approaches also cannot easily differentiate between living and dead bacteria. Two emerging tools will be leveraged to obtain this information: (1) gas-reporting biosensors that report on in situ conjugation events; and (2) a high-throughput, culture-independent method for determining the host-range of ARGs in a mixed community. These tools will be applied in bioreactors treating domestic wastewater to better understand how operational controls impact ARG propagation rates and host range. The objectives of this research are to (1) develop biosensors that report on HGT in situ by coupling the synthesis of an enzyme that produces a rare volatile gas to broad-range plasmid transfer; (2) use these tools in bench-scale wastewater bioreactors to monitor HGT rates across a community under various reactor conditions; and (3) characterize the host range of the engineered plasmids and of a suite of environmentally-relevant ARGs under different bioreactor operational conditions. The results of this research will advance the knowledge of the mechanisms that govern HGT of ARGs in wastewater treatment and water reuse systems that will inform management strategies to protect human health.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

A major technological revolution is emerging as researchers develop the ability to interface natural and synthetic cellular systems with nanoscale materials to create hybrid cells and devices that communicate electronically. This new interdisciplinary field has the potential to transform fundamental science, industry, medicine, and our way of life. To achieve these innovations, industry will require a workforce that collaborates across disciplines to develop devices that enable measurement, manipulation, control and sensing of biological processes of organisms, cells, molecules and reactions. Because this industry will change how we interact with each other, this topic will present new policy, economic, and environmental issues to solve. The National Science Foundation Research Traineeship (NRT) award to William Marsh Rice University will address these challenges by training graduate doctoral students in the interdisciplinary field of bioelectronics. The project anticipates training thirty (30) doctoral students, including eighteen (18) funded trainees, from engineering, natural sciences, and social sciences doctoral programs.

Students typically begin training in disciplinary graduate programs, and collaboration follows after investing significant time into defining the research problem, often through co-mentored apprenticeships. This educational model is thought to limit the kinds of questions that students pursue because students are not poised to effectively integrate into the type of teams required for bioelectronics innovation. To overcome these limitations, this NRT program will integrate a team-first pedagogical model for doctoral training with bioelectronics research to educate students about past interdisciplinary innovations, theoretical underpinnings of interdisciplinarity, creation of cohesive teams and community building, frameworks for achieving conceptual understanding across disciplines, and strategies to understand the needs of stakeholders. Research activities centered on bioelectronics themes encompass diverse topics, such as light-harvesting systems that enable chemical synthesis within cells, instruments that monitor complex electrical signaling in the nervous system, and living sensors that interface with handheld devices. This traineeship program will also provide training in effective communication, teaching and mentorship, conflict resolution, leadership and management, responsible conduct in research, and outreach. Students will work in interdisciplinary teams to identify bioelectronics questions, perform team-based research, and generate joint publications. Team integration will be achieved through catalysts, including the synthesis of proposals and articles, the creation of activities for educating others about interdisciplinarity, interdisciplinary workshops, peer-writing groups, cell/device fabrication and testing activities, and annual activities that refine interdisciplinary communication skills.

The NSF Research Traineeship (NRT) Program is designed to encourage the development and implementation of bold, new potentially transformative models for STEM graduate education training. The program is dedicated to effective training of STEM graduate students in high priority interdisciplinary research areas through comprehensive traineeship models that are innovative, evidence-based, and aligned with changing workforce and research needs.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Cells utilize many chemical sources of energy. Photosynthetic cells can use sunlight to create chemical bonds that store energy. That energy is used to shuttle electrons around the cell, driving reactions. Despite that, cells cannot utilize external sources of electrical energy directly. If they could utilize electricity as a power source, that would greatly reduce the burden on the cell to create energy on site, freeing it to be directed to more productive activities. This project is an attempt to create a cellular interface that allows that to happen. The external power source will be electricity generated by solar panels. The electricity will drive the production of an amino acid. Graduate students and undergraduates will be trained in advanced bioelectronics research techniques.


The goal of this project is to build a modular cell-material interface that couples external electrical energy sources to the reduction of ferredoxins. The material side of the interface will enable attachment to a range of energy harvesting devices. The cell side will facilitate the transport of low potential electrons across the cell membrane to a ferredoxin, which will then be used to enhance the production of a reduced metabolite, the amino acid cysteine. The first objective is to engineer efficient electron transfer across the membrane. A high-throughput selection will be used to couple the growth of Escherichia coli to the electron cycling efficiency of low potential ferredoxin (Fd) electron carriers. The second objective is to build a biocompatible material (an organic electrode) that functions as a cell-surface coupling module. Diffusible mediators will be incorporated into the electrode and the effectiveness of organic phospholipids in mediating long-range electron transfer will be examined. The final objective is to use biological-organic hybrids to increase metabolic pathway yields and characterize electron transfer efficiencies. The interfaces arising from this project will be modular, and potentially useful in powering natural and synthetic cell processes.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Computers use two mechanisms to store data: read-only memory (ROM), which can be written but not erased, and random-access memory (RAM), which can be written and erased multiple times. Cells can also be programmed to store high density read-only data by permanently modifying the genetic code, and they have the potential to be used as sustainable data storage components for digital devices. However, it remains challenging to store high density data in cells using RAM-like approaches that allow for multiple write-read-erase cycles. In addition, there are limited methods to read out stored biological information non-disruptively, without affecting cell viability. To overcome these challenges, this project will code information into different biomolecules within cells, including synthetic RNA, which are retained within cells, and redox-active small molecules, which can diffuse in and out of cells. Outside of cells, the mediators will be detected using semiconducting polymers which represent sustainable bio-materials. All of these components will be assembled to build a hybrid biological-semiconductor system with high storage and communication functionalities. This research will train doctoral students pursuing studies in multiple disciplines to work effectively in interdisciplinary teams, and it will educate scholars at community colleges about research and transfer opportunities. <br/><br/>The goal of this research is to create hybrid cell-material systems capable of high-density data storage in cells (100 bytes) using RNA, with facile read out through the bio-production of redox-active chemical mediators. These systems will be created by programming cells to synthesize mediator components, by using a facile low energy electrochemical read out, and by decoding information from living cells in a manner that minimizes cell fitness burdens and data storage failure rates. Additive manufacturing approaches will be developed to achieve scalable and sustainable biohybrid systems. Two novel forms of biological memory elements will be used to create random-access memory that is capable of repetitive write-read-erase data cycles. First, RNA memory will be created that codes data using a highly designable catalytic RNA. Second, mediator memory will be created that can be read out using a semiconductive polymer outside of cells. The proof-of-concept bioelectronic system will be created using the model microbe Escherichia coli. The modularity of the memory elements will then be evaluated in other gram-negative microbes to establish how portable these approaches are across different cellular chassis.<br/><br/>This project has been jointly funded by Division of Molecular and Cellular Biosciences (MCB) in the Directorate for Biological Sciences (BIO), Division of Computing and Communication Foundations (CCF) in the Directorate for Computer and Information Science and Engineering (CISE), Division of Electrical, Communications and Cyber Systems (ECCS) in the Directorate for Engineering (ENG), and the Division of Materials Research (DMR) in the Directorate for Mathematical and Physical Sciences (MPS).<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.