Senior Research Fellow & Group Lead
Overview
Rosemary Cater was recently recruited to UQ's Institute for Molecular Bioscience as a Group Leader and ARC DECRA Fellow. She utilizes structural biology, membrane protein biochemistry, and biophysics to understand some of the brain’s most elusive yet important proteins. The overarching goal of the Cater Lab is to understand molecular mechanisms of transport at the blood-brain barrier.
Dr. Cater was awarded her PhD in 2017 from the University of Sydney, and from 2017-2023 she was a Post-Doctoral Fellow in the laboratory of Prof. Filippo Mancia at Columbia University, New York, USA. Here she used single-particle cryo-electron microscopy and antigen-binding technology to determine structures of small membrane proteins.
Highlights of her career thus far include:
- She has been awarded an ARC DECRA, an NIH K99/R00 career transition award.
- She received a 2022 Blavatnik Regional Finalist Award in Chemistry – a highly competitive award for outstanding post-doctoral research presented at the New York Academy of Sciences Annual Gala.
- She was selected as one was 1 of 120 young leaders invited from 46 countries to the 2022 Science and Technology in Society Forum (Kyoto) to discuss humanity’s global challenges with politicians, CEOs, and Nobel Laureates.
- She was appointed as one of twelve Simons Society Fellows (2018-2022) – one of the USA’s most competitive post-doctoral fellowships, founded in New York by billionaire philanthropist Jim Simons.
- She received a Robin Anders Young Investigator Award at the Lorne Protein Structure and Function 2020 Meeting – one of Australia’s most competitive awards for early-career protein scientists.
Research Interests
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Molecular mechanisms of blood-brain barrier transport
The blood-brain barrier (BBB) is a highly selective semipermeable barrier that separates the blood from the brain. It plays a critical role in maintaining homeostasis in the brain and the activation of the central nervous system. Transporters expressed at the BBB serve as the gatekeepers of this boundary, selectively allowing the passage of essential nutrients into the brain while preventing the entry of potentially harmful substances. While this barrier evolved to protect our brains from harm, it also prevents ~98% of all small-molecule drugs from entering the brain. This creates a major bottleneck in the development of treatments for brain diseases such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, anxiety, and depression. The overarching goal of the Cater Lab is to understand the molecular mechanisms of transport at the blood-brain barrier. We employ a multidisciplinary approach, encompassing cryo-electron microscopy (cryo-EM), biochemistry, and biophysics to unravel the molecular details underpinning how transporters at the BBB allow specific molecules to cross this barrier. By dissecting these mechanisms, we hope to not only understand more about how the brain acquires nutrients critical for its function but also to provide insights into designing neurotherapeutics so that they can be smuggled into the brain via these transporters.
Research Impacts
Dr. Cater strive to excel as an academic beyond the bench. She has served on organising committees for the USA Biophysical Society Cryo-EM subgroup meeting (2023) and Lorne Proteins (2024 onward). She has reviewed articles for 10 journals including Cell, Nature Structure and Molecular Biology, Nature Communications, and eLife. She has presented seminars at rural high schools about 'Science at University and a career in Research" and mentored students from the Columbia University Program for Under-Represented Students to improve STEM diversity/inclusion. She has co-supervised 9 students (3 PhD, 1 Honours, 6 undergraduates) at Columbia and Sydney University, and taught undergraduate/postgraduate workshops and labs.
Qualifications
- Doctoral (Research) of Pharmacology, University of Sydney
- Bachelor (Honours) of Biochemistry, University of Sydney
Publications
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Journal Article: Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A
Bergman, Shana, Cater, Rosemary J., Plante, Ambrose, Mancia, Filippo and Khelashvili, George (2023). Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A. Nature Communications, 14 (1) 3391. doi: 10.1038/s41467-023-39088-y
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Journal Article: Structural insights into transporter-mediated drug resistance in infectious diseases
Kim, Jonathan, Cater, Rosemary J., Choy, Brendon C. and Mancia, Filippo (2021). Structural insights into transporter-mediated drug resistance in infectious diseases. Journal of Molecular Biology, 433 (16) 167005, 1-24. doi: 10.1016/j.jmb.2021.167005
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Journal Article: Structural basis of omega-3 fatty acid transport across the blood-brain barrier
Cater, Rosemary J., Chua, Geok Lin, Erramilli, Satchal K., Keener, James E., Choy, Brendon C., Tokarz, Piotr, Chin, Cheen Fei, Quek, Debra Q. Y., Kloss, Brian, Pepe, Joseph G., Parisi, Giacomo, Wong, Bernice H., Clarke, Oliver B., Marty, Michael T., Kossiakoff, Anthony A., Khelashvili, George, Silver, David L. and Mancia, Filippo (2021). Structural basis of omega-3 fatty acid transport across the blood-brain barrier. Nature, 595 (7866), 315-319. doi: 10.1038/s41586-021-03650-9
Grants
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How does heme regulate blood vessel formation in the brain?
(2023–2026) ARC Discovery Early Career Researcher Award
Available Projects
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Characterization of blood-brain barrier nutrient transporters
The blood-brain barrier (BBB) is a layer of tightly packed endothelial cells that separate the blood for the brain. The BBB has evolved to protect our brains from blood-borne neurotoxins and pathogens, but unfortunately, it also prevents the majority of potential neurotherapeutics from entering the brain. In fact, it has been estimated that ~98% of all small-molecule drugs are not able to cross the BBB. This creates a major bottleneck in the development of treatments for diseases such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, anxiety, and depression. The more we know about what can enter the brain, the better informed we will be for developing treatments for these diseases. Transporter proteins expressed at the BBB play a very important role in regulating the entrance of molecules in a highly specific manner. For example, the transporters FLVCR2 and MFSD2A allow for the uptake of choline and omega-3 fatty acids into the brain – both of which are essential nutrients that the brain requires in very large amounts. This project will utilise biochemical techniques and structural biology (cryo-EM) to further understand transport proteins at the BBB and how they transport specific molecules into the brain. This will provide critical insights that for the development of neurotherapeutics that can hijack these transporters to allow for entrance into the brain.
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Understanding how blood vessels in the brain are formed
The human brain comprises ~650 kilometres of blood vessels lined by brain endothelial cells, which supply the brain with oxygen and essential nutrients. The growth of cerebral blood vessels begins early in development via a process called sprouting angiogenesis. Despite its importance, the molecular mechanisms underlying brain angiogenesis and formation of the blood-brain barrier are poorly understood. It has recently been demonstrated that the gene Flvcr2 is critical for blood vessels to grow in the brain, and last year we discovered that the protein encoded by this gene (FLVCR2) transports choline – an essential nutrient – across the blood brain barrier and into the brain. This project will utilise biochemical techniques and structural biology (cryo-EM) to investigate what other molecules may regulate this transport process, and how choline regulates angiogenesis in the brain.
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Understanding the molecular structures of proteins involved in rare disease.
Rare diseases are often caused by genetic mutations that disrupt protein function. In some cases, we already understand the three-dimensional structure and functional role of these proteins in healthy individuals. However, unfortunately, for some rare diseases, we lack this knowledge. This lack of information prevents us from understanding how mutations within the protein can lead to malfunction and disease onset, which in turn prevents us from understanding the disease and how to treat it. This project will employ biochemical techniques, structural biology (cryo-EM), and computational approaches to understand the normal 3D structure and role of proteins implicated in rare diseases. By elucidating these aspects, we will provide critical insights for the development of drugs to treat these rare diseases.
Publications
Journal Article
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Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A
Bergman, Shana, Cater, Rosemary J., Plante, Ambrose, Mancia, Filippo and Khelashvili, George (2023). Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A. Nature Communications, 14 (1) 3391. doi: 10.1038/s41467-023-39088-y
-
Structural insights into transporter-mediated drug resistance in infectious diseases
Kim, Jonathan, Cater, Rosemary J., Choy, Brendon C. and Mancia, Filippo (2021). Structural insights into transporter-mediated drug resistance in infectious diseases. Journal of Molecular Biology, 433 (16) 167005, 1-24. doi: 10.1016/j.jmb.2021.167005
-
Structural basis of omega-3 fatty acid transport across the blood-brain barrier
Cater, Rosemary J., Chua, Geok Lin, Erramilli, Satchal K., Keener, James E., Choy, Brendon C., Tokarz, Piotr, Chin, Cheen Fei, Quek, Debra Q. Y., Kloss, Brian, Pepe, Joseph G., Parisi, Giacomo, Wong, Bernice H., Clarke, Oliver B., Marty, Michael T., Kossiakoff, Anthony A., Khelashvili, George, Silver, David L. and Mancia, Filippo (2021). Structural basis of omega-3 fatty acid transport across the blood-brain barrier. Nature, 595 (7866), 315-319. doi: 10.1038/s41586-021-03650-9
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Glutamate transporters have a chloride channel with two hydrophobic gates
Chen, Ichia, Pant, Shashank, Wu, Qianyi, Cater, Rosemary J., Sobti, Meghna, Vandenberg, Robert J., Stewart, Alastair G., Tajkhorshid, Emad, Font, Josep and Ryan, Renae M. (2021). Glutamate transporters have a chloride channel with two hydrophobic gates. Nature, 591 (7849), 327-331. doi: 10.1038/s41586-021-03240-9
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Choy, Brendon C., Cater, Rosemary J., Mancia, Filippo and Pryor, Edward E. (2021). A 10-year meta-analysis of membrane protein structural biology: detergents, membrane mimetics, and structure determination techniques. Biochimica Et Biophysica Acta Biomembranes, 1863 (3) 183533, 183533. doi: 10.1016/j.bbamem.2020.183533
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Krycer, James R., Fazakerley, Daniel J., Cater, Rosemary J., Thomas, Kristen C., Naghiloo, Sheyda, Burchfield, James G., Humphrey, Sean J., Vandenberg, Robert J., Ryan, Renae M. and James, David E. (2017). The amino acid transporter, SLC1A3, is plasma membrane-localised in adipocytes and its activity is insensitive to insulin. FEBS Letters, 591 (2), 322-330. doi: 10.1002/1873-3468.12549
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Tuning the ion selectivity of glutamate transporter-associated uncoupled conductances
Cater, Rosemary J., Vandenberg, Robert J. and Ryan, Renae M. (2016). Tuning the ion selectivity of glutamate transporter-associated uncoupled conductances. Journal of General Physiology, 148 (1), 13-24. doi: 10.1085/jgp.201511556
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The split personality of glutamate transporters: a chloride channel and a transporter
Cater, Rosemary J., Ryan, Renae M. and Vandenberg, Robert J. (2016). The split personality of glutamate transporters: a chloride channel and a transporter. Neurochemical Research, 41 (3), 593-599. doi: 10.1007/s11064-015-1699-6
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The domain interface of the human glutamate transporter EAAT1 mediates chloride permeation
Cater, Rosemary J., Vandenberg, Robert J. and Ryan, Renae M. (2014). The domain interface of the human glutamate transporter EAAT1 mediates chloride permeation. Biophysical Journal, 107 (3), 621-629. doi: 10.1016/j.bpj.2014.05.046
Grants (Administered at UQ)
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How does heme regulate blood vessel formation in the brain?
(2023–2026) ARC Discovery Early Career Researcher Award
Possible Research Projects
Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.
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Characterization of blood-brain barrier nutrient transporters
The blood-brain barrier (BBB) is a layer of tightly packed endothelial cells that separate the blood for the brain. The BBB has evolved to protect our brains from blood-borne neurotoxins and pathogens, but unfortunately, it also prevents the majority of potential neurotherapeutics from entering the brain. In fact, it has been estimated that ~98% of all small-molecule drugs are not able to cross the BBB. This creates a major bottleneck in the development of treatments for diseases such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, anxiety, and depression. The more we know about what can enter the brain, the better informed we will be for developing treatments for these diseases. Transporter proteins expressed at the BBB play a very important role in regulating the entrance of molecules in a highly specific manner. For example, the transporters FLVCR2 and MFSD2A allow for the uptake of choline and omega-3 fatty acids into the brain – both of which are essential nutrients that the brain requires in very large amounts. This project will utilise biochemical techniques and structural biology (cryo-EM) to further understand transport proteins at the BBB and how they transport specific molecules into the brain. This will provide critical insights that for the development of neurotherapeutics that can hijack these transporters to allow for entrance into the brain.
-
Understanding how blood vessels in the brain are formed
The human brain comprises ~650 kilometres of blood vessels lined by brain endothelial cells, which supply the brain with oxygen and essential nutrients. The growth of cerebral blood vessels begins early in development via a process called sprouting angiogenesis. Despite its importance, the molecular mechanisms underlying brain angiogenesis and formation of the blood-brain barrier are poorly understood. It has recently been demonstrated that the gene Flvcr2 is critical for blood vessels to grow in the brain, and last year we discovered that the protein encoded by this gene (FLVCR2) transports choline – an essential nutrient – across the blood brain barrier and into the brain. This project will utilise biochemical techniques and structural biology (cryo-EM) to investigate what other molecules may regulate this transport process, and how choline regulates angiogenesis in the brain.
-
Understanding the molecular structures of proteins involved in rare disease.
Rare diseases are often caused by genetic mutations that disrupt protein function. In some cases, we already understand the three-dimensional structure and functional role of these proteins in healthy individuals. However, unfortunately, for some rare diseases, we lack this knowledge. This lack of information prevents us from understanding how mutations within the protein can lead to malfunction and disease onset, which in turn prevents us from understanding the disease and how to treat it. This project will employ biochemical techniques, structural biology (cryo-EM), and computational approaches to understand the normal 3D structure and role of proteins implicated in rare diseases. By elucidating these aspects, we will provide critical insights for the development of drugs to treat these rare diseases.
