Gia Voeltz

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Gia Voeltz
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Born
Gia Voeltz

Bloomington, Indiana, United States
Alma mater University of California Santa Cruz (BS)
Yale University (PhD)
Harvard Medical School (Postdoctoral)
Known fordiscovering the function of the Reticulon protein family
AwardsMember: National Academy of Sciences 2023
Fellow: American Society for Cell Biology 2023
Investigator: Howard Hughes Medical Institute 2018
Scholar: Howard Hughes Medical Institute 2016
Scientific career
Fields
Institutions
Thesis mRNA Stability is Regulated during Early Development by AU-rich Sequences and a Novel Poly(A) Binding Protein, ePAB  (2001)
Doctoral advisor Joan A. Steitz

Gia Voeltz is an American cell biologist. She is a professor of Molecular, Cellular and Developmental Biology at the University of Colorado Boulder and a Howard Hughes Medical Institute Investigator. She is known for her research identifying the factors and unraveling the mechanisms that determine the structure and dynamics of the largest organelle in the cell: the endoplasmic reticulum. [1] [2] Her lab has produced paradigm shifting studies on organelle membrane contact sites that have revealed that most cytoplasmic organelles are not isolated entities but are instead physically tethered to an interconnected ER membrane network. [3] [4] [5]

Contents

Her research has revealed the fundamental nature of these ER contact sites in regulating the biogenesis of other organelles at positions where they are tethered and closely opposed. [6] [7] [8] [9]

Early life and education

Gia Voeltz grew up in several different states including Indiana, Hawaii, Minnesota and Upstate New York, where she graduated from Chenango Forks High School. She attended university at the University of California Santa Cruz where she majored in Biochemistry and Molecular Biology. She performed her senior thesis work in the lab of Manny Ares [10] on pre-spliceosome assembly in yeast. [11] This experience in the Ares lab at UC Santa Cruz inspired her to become a scientist. Her early undergraduate research studying RNA processing led her to pursue a PhD thesis in the Department of Molecular Biophysics and Biochemistry at Yale University in the lab of Joan A. Steitz, a leading figure in RNA biology. Her PhD research investigated how mRNA stability was regulated during different stages of early development using Xenopus eggs and extract as a model system. [12] [13]

She then moved to Harvard Medical School to join the lab of Tom Rapoport as a Jane Coffin Childs postdoctoral fellow.

Career

Gia Voeltz was trained as an RNA biologist but made a major switch in scientific sub-fields when she moved to Tom Rapoport’s lab as a postdoc to study how organelles get their shape. As a postdoc, she set out to identify how membrane proteins generate the elaborate shape of the ER. To do this, she used biochemical fractionation of a Xenopus egg in vitro assay for ER network formation. [14] Her postdoctoral studies identified the Reticulon family of ER membrane proteins and demonstrated their conserved role in generating the structure of the tubular ER network. [2] The hairpin "wedge" mechanism proposed was that Reticulon has two short hairpin transmembrane domains that occupy more area in the outer leaflet to generate the high membrane curvature found in tubules. [2]

Gia Voeltz moved to University of Colorado Boulder in 2006 [15] to start her own lab. Her lab leveraged spinning disk confocal microscopy to visualize the reticulon-generated dynamic tubular ER network in live cells at high resolution. [3] This led to the observation that ER tubule dynamics often occurred at positions where the ER tubules were tightly tethered to other dynamic organelles like endosomes and mitochondria. [3] [4]

Multi-color live cell fluorescence imaging complemented by high resolution electron microscopy and tomography revealed that the vast majority of endosomes and mitochondria are tethered to the ER at contact sites. In a hallmark paper published in 2011, Voeltz lab, in a collaboration with Jodi Nunnari’s lab, showed that ER tubules wrap around mitochondria to define the position where mitochondria constrict and divide in animal and yeast cells. [6]

Her lab has gone on to show that ER contact sites also regulate early and late endosome fission, [7] [8] RNA granule division, [9] and mitochondrial fusion. [16] [17] These works establish the ER network as a master regulator of organelle biogenesis through ER contact sites. [5] [18]

Gia Voeltz became a Howard Hughes Medical Institute Scholar in 2016 [19] and a Howard Hughes Medical Institute Investigator in 2018. [20] [21] She was elected to the National Academy of Sciences in 2023. [22]

Awards and honors

Institutions

Related Research Articles

Cell biology is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and functioning of organisms. Cell biology is the study of the structural and functional units of cells. Cell biology encompasses both prokaryotic and eukaryotic cells and has many subtopics which may include the study of cell metabolism, cell communication, cell cycle, biochemistry, and cell composition. The study of cells is performed using several microscopy techniques, cell culture, and cell fractionation. These have allowed for and are currently being used for discoveries and research pertaining to how cells function, ultimately giving insight into understanding larger organisms. Knowing the components of cells and how cells work is fundamental to all biological sciences while also being essential for research in biomedical fields such as cancer, and other diseases. Research in cell biology is interconnected to other fields such as genetics, molecular genetics, molecular biology, medical microbiology, immunology, and cytochemistry.

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that synthesizes, folds and processes proteins

The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae, and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.

<span class="mw-page-title-main">Endomembrane system</span> Membranes in the cytoplasm of a eukaryotic cell

The endomembrane system is composed of the different membranes (endomembranes) that are suspended in the cytoplasm within a eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles. In eukaryotes the organelles of the endomembrane system include: the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, lysosomes, vesicles, endosomes, and plasma (cell) membrane among others. The system is defined more accurately as the set of membranes that forms a single functional and developmental unit, either being connected directly, or exchanging material through vesicle transport. Importantly, the endomembrane system does not include the membranes of plastids or mitochondria, but might have evolved partially from the actions of the latter.

<span class="mw-page-title-main">Endocytosis</span> Cellular process

Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested materials. Endocytosis includes pinocytosis and phagocytosis. It is a form of active transport.

<span class="mw-page-title-main">Golgi apparatus</span> Cell organelle that packages proteins for export

The Golgi apparatus, also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destination. It resides at the intersection of the secretory, lysosomal, and endocytic pathways. It is of particular importance in processing proteins for secretion, containing a set of glycosylation enzymes that attach various sugar monomers to proteins as the proteins move through the apparatus.

<span class="mw-page-title-main">Peroxisome</span> Type of organelle

A peroxisome (IPA:[pɛɜˈɹɒksɪˌsoʊm]) is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen peroxide (H2O2) is then formed. Peroxisomes owe their name to hydrogen peroxide generating and scavenging activities. They perform key roles in lipid metabolism and the reduction of reactive oxygen species.

Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.

<span class="mw-page-title-main">Vesicle (biology and chemistry)</span> Any small, fluid-filled, spherical organelle enclosed by a membrane

In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis), and the transport of materials within the plasma membrane. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, the vesicles are called unilamellar liposomes; otherwise they are called multilamellar liposomes. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.

A signal peptide is a short peptide present at the N-terminus of most newly synthesized proteins that are destined toward the secretory pathway. These proteins include those that reside either inside certain organelles, secreted from the cell, or inserted into most cellular membranes. Although most type I membrane-bound proteins have signal peptides, most type II and multi-spanning membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which biochemically resembles a signal sequence except that it is not cleaved. They are a kind of target peptide.

<span class="mw-page-title-main">Outline of cell biology</span> Overview of and topical guide to cell biology

The following outline is provided as an overview of and topical guide to cell biology:

Reticulons are a group of evolutionary conservative proteins residing predominantly in endoplasmic reticulum, primarily playing a role in promoting membrane curvature. In addition, reticulons may play a role in nuclear pore complex formation, vesicle formation, and other processes yet to be defined. They have also been linked to oligodendrocyte roles in inhibition of neurite outgrowth. Some studies link RTNs with Alzheimer's disease and amyotrophic lateral sclerosis.

Membrane contact sites (MCS) are close appositions between two organelles. Ultrastructural studies typically reveal an intermembrane distance in the order of the size of a single protein, as small as 10 nm or wider, with no clear upper limit. These zones of apposition are highly conserved in evolution. These sites are thought to be important to facilitate signalling, and they promote the passage of small molecules, including ions, lipids and reactive oxygen species. MCS are important in the function of the endoplasmic reticulum (ER), since this is the major site of lipid synthesis within cells. The ER makes close contact with many organelles, including mitochondria, Golgi, endosomes, lysosomes, peroxisomes, chloroplasts and the plasma membrane. Both mitochondria and sorting endosomes undergo major rearrangements leading to fission where they contact the ER. Sites of close apposition can also form between most of these organelles most pairwise combinations. First mentions of these contact sites can be found in papers published in the late 1950s mainly visualized using electron microscopy (EM) techniques. Copeland and Dalton described them as “highly specialized tubular form of endoplasmic reticulum in association with the mitochondria and apparently in turn, with the vascular border of the cell”.

<span class="mw-page-title-main">Jennifer Lippincott-Schwartz</span> American biologist

Jennifer Lippincott-Schwartz is a Senior Group Leader at Howard Hughes Medical Institute's Janelia Research Campus and a founding member of the Neuronal Cell Biology Program at Janelia. Previously, she was the Chief of the Section on Organelle Biology in the Cell Biology and Metabolism Program, in the Division of Intramural Research in the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health from 1993 to 2016. Lippincott-Schwartz received her PhD from Johns Hopkins University, and performed post-doctoral training with Richard Klausner at the NICHD, NIH in Bethesda, Maryland.

<span class="mw-page-title-main">Tom Rapoport</span> German-American cell biologist (born 1947)

Tom Abraham Rapoport is a German-American cell biologist who studies protein transport in cells. Currently, he is a professor at Harvard Medical School and a Howard Hughes Medical Institute investigator. Born in Cincinnati, Ohio, he grew up in East Germany. In 1995 he accepted an offer to become a professor at Harvard Medical School. In 1997 he became an investigator of the Howard Hughes Medical Institute. He is a member of the American and German National Academies of Science.

A target peptide is a short peptide chain that directs the transport of a protein to a specific region in the cell, including the nucleus, mitochondria, endoplasmic reticulum (ER), chloroplast, apoplast, peroxisome and plasma membrane. Some target peptides are cleaved from the protein by signal peptidases after the proteins are transported.

Transmembrane protein 33 is a protein that in humans, is encoded by the TMEM33 gene, also known as SHINC3. Another name for the TMEM33 protein is DB83.

DP1/Yop1p is an integral membrane protein family that, along with the reticulons, is responsible for the shape of the tubular endoplasmic reticulum (ER) in yeast and mammalian cells. Furthermore, it is also believed that they might be involved in sheet ER formation.

<span class="mw-page-title-main">Intracellular transport</span> Directed movement of vesicles and substances within a cell

Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are distributed to their respective organelles, according to their specific amino acid’s sorting sequence. Eukaryotic cells transport packets of components to particular intracellular locations by attaching them to molecular motors that haul them along microtubules and actin filaments. Since intracellular transport heavily relies on microtubules for movement, the components of the cytoskeleton play a vital role in trafficking vesicles between organelles and the plasma membrane by providing mechanical support. Through this pathway, it is possible to facilitate the movement of essential molecules such as membrane‐bounded vesicles and organelles, mRNA, and chromosomes.

<span class="mw-page-title-main">Star related lipid transfer domain containing 3</span>

StAR related lipid transfer domain containing 3(STARD3) is a protein that in humans is encoded by the STARD3 gene. STARD3 also known as metastatic lymph node 64 protein (MLN64) is a late endosomal integral membrane protein involved in cholesterol transport. STARD3 creates membrane contact sites between the endoplasmic reticulum (ER) and late endosomes where it moves cholesterol.

The TIGER domain is a minor membraneless organelle in which messenger RNA (mRNA) encodes certain types of proteins to find the appropriate environment for growth. It is closely associated with the endoplasmic reticulum during protein synthesis. The TIGER domain was first documented by cell biologists Christine Mayr and Weirui Ma at the Gerstner Sloan Kettering Graduate School of Biomedical Sciences in 2018.

References

  1. ↑ Westrate LM, Lee JE, Prinz WA, Voeltz GK (January 2015). "Form follows function: the importance of endoplasmic reticulum shape". Annual Review of Biochemistry. 84: 791–811. doi:10.1146/annurev-biochem-072711-163501. PMID   25580528. S2CID   207675243.
  2. 1 2 3 Voeltz GK, Prinz WA, Shibata Y, Rist JM, Rapoport TA (10 February 2006). "A class of membrane proteins shaping the tubular endoplasmic reticulum". Cell. 124 (3): 573–586. doi: 10.1016/j.cell.2005.11.047 . PMID   16469703.
  3. 1 2 3 Friedman JR, Webster BM, Mastronarde DN, Verhey KJ, Voeltz GK (9 August 2010). "ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules". Journal of Cell Biology. 190 (3): 363–375. doi:10.1083/jcb.200911024. PMC   2922647 . PMID   20696706.
  4. 1 2 Friedman JR, Dibenedetto JR, West M, Rowland AA, Voeltz GK (6 February 2013). "Endoplasmic reticulum-endosome contact increases as endosomes traffic and mature". Molecular Biology of the Cell. 24 (7): 1030–1040. doi:10.1091/mbc.E12-10-0733. PMC   3608491 . PMID   23389631.
  5. 1 2 Wu H, Carvalho P, Voeltz GK (3 August 2018). "Here, there, and everywhere: The importance of ER membrane contact sites". Science. 361 (6401). doi:10.1126/science.aan5835. PMC   6568312 . PMID   30072511.
  6. 1 2 Friedman JR, Lackner LL, West M, Dibenedetto JR, Nunnari J, Voeltz GK (21 October 2011). "ER tubules mark sites of mitochondrial division". Science. 334 (6954): 358–362. Bibcode:2011Sci...334..358F. doi:10.1126/science.1207385. PMC   3366560 . PMID   21885730.
  7. 1 2 Rowland AA, Chitwood PJ, Phillips MJ, Voeltz GK (20 November 2014). "ER contact sites define the position and timing of endosome fission". Cell. 159 (5): 1027–1041. doi:10.1016/j.cell.2014.10.023. PMC   4634643 . PMID   25416943.
  8. 1 2 Hoyer MJ, Chitwood PJ, Ebmeier CC, Striepen JF, Qi RZ, Old WM, Voeltz GK (13 September 2018). "A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission". Cell. 175 (1): 254–265. doi:10.1016/j.cell.2018.08.030. PMC   6195207 . PMID   30220460.
  9. 1 2 Lee JE, Cathey PI, Wu H, Parker R, Voeltz GK (31 January 2020). "Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles". Science. 367 (6477). doi:10.1126/science.aay7108. PMC   10088059 . PMID   32001628.
  10. ↑ Perriman R, Barta I, Voeltz GK, Abelson J, Ares M (10 November 2003). "ATP requirement for Prp5p function is determined by Cus2p and the structure of U2 small nuclear RNA". Proceedings of the National Academy of Sciences of the United States of America. 100 (24): 13857–13862. Bibcode:2003PNAS..10013857P. doi: 10.1073/pnas.2036312100 . PMC   283511 . PMID   14610285.
  11. ↑ Voeltz GK, Steitz JA (23 August 1998). "AUUUA Sequences Direct mRNA Deadenylation Uncoupled from Decay during Xenopus Early Development". Molecular and Cellular Biology. 18 (12): 7537–7545. doi:10.1128/MCB.18.12.7537. PMC   109334 . PMID   9819439.
  12. ↑ Voeltz GK, Ongkasuwan J, Standart N, Steitz JA (15 March 2001). "A novel embryonic poly(A) binding protein, ePAB, regulates mRNA deadenylation in Xenopus egg extracts". Genes & Development. 15 (6): 774–788. doi:10.1101/gad.872201. PMC   312653 . PMID   11274061.
  13. ↑ Dreier L, Rapoport TA (6 March 2000). "In vitro formation of the endoplasmic reticulum occurs independently of microtubules by a controlled fusion reaction". Journal of Cell Biology. 148 (5): 883–898. doi:10.1083/jcb.148.5.883. PMC   2174540 . PMID   10704440.
  14. ↑ Voeltz GK, Cheeseman I (13 October 2017). "Building a path in cell biology". Molecular Biology of the Cell. 23 (21): 4145–4147. doi:10.1091/mbc.E12-05-0382. PMC   3484087 . PMID   23112222.
  15. ↑ Abrisch RG, Gumbin SC, Wisniewski BT, Lackner LL, Voeltz GK (25 February 2020). "Fission and fusion machineries converge at ER contact sites to regulate mitochondrial morphology". Journal of Cell Biology. 219 (4). doi:10.1083/jcb.201911122. PMC   7147108 . PMID   32328629.
  16. ↑ Nguyen TT, Voeltz and GK (30 Nov 2022). "An ER phospholipid hydrolase drives ER-associated mitochondrial constriction for fission and fusion". eLife. 11. doi: 10.7554/eLife.84279 . PMC   9725753 . PMID   36448541.
  17. ↑ Voeltz, Gia (speaker) (22 May 2019). Factors and Functions of Organelle Membrane Contact Sites. iBiology. Retrieved 18 January 2024– via Youtube.
  18. 1 2 "HHMI 2016 Faculty Scholars". HHMI. Retrieved 18 January 2024.
  19. ↑ "HHMI Bets Big On 19 New Investigators". HHMI. 23 May 2018. Retrieved 18 January 2024.
  20. 1 2 "Cellular cartographer Voeltz named HHMI investigator, granted $8 million". University of Colorado Boulder. 23 May 2018. Retrieved 18 January 2024.
  21. 1 2 "Pioneering biologist elected to National Academy of Sciences". University of Colorado Boulder. 12 May 2023. Retrieved 18 January 2024.
  22. ↑ "Gia K. Voeltz". nasonline.org. National Academy of Sciences. Retrieved 18 Jan 2024.
  23. ↑ "Nineteen distinguished scientists recognized as 2023 ASCB Fellows". ascb.org. American Society for Cell Biology. 2 August 2023. Retrieved 18 Jan 2024.
  24. ↑ "Günter Blobel Early Career Award". ascb.org. American Society for Cell Biology. 2012. Retrieved 18 January 2024.
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