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Staff profile

Overview

Dr Ting-Yu Lin

Assistant Professor

Affiliations
Affiliation
Assistant Professor in the Department of Biosciences

Biography

Ting-Yu Lin completed her bachelor's training in Medical Laboratory Science and Biotechnology at Taipei Medical University in Taiwan in 2004, and she then enrolled in the Ph.D. program at the Department of Clinical Laboratory Sciences and Medical Biotechnology at National Taiwan University, where she studied the anti-cancer effects and mechanisms of natural compounds extract. During her PhD, she received the PhD exchanging 1-year scholarship to expand her experience in RNA splicing in City of Hope/Bachman Research Institute in California, US. After obtaining PhD, she worked as a postdoctoral fellow at RIKEN Japan, where she started biochemical and structural investigations on gyrases. She later moved to join a Max Planck research group at Malopolska Center Biotechnology/Jagiellonian University in Poland, where she investigated several tRNA modifying enzymes regarding their biochemical features and cryo-EM structures.

Research Interests
  • Structural Biology
  • Biochemistry
  • Molecular Biology

RNA modification is a way to expand the RNA nucleotide structure and function capacity, which tightly correlates to regulating several cellular events (i.e., translation). Pseudouridine, one of the most abundant modifications, was the first discovered RNA modification. It is ubiquitous and present in many RNA classes. It serves the role of maintaining RNA structure stability, which mediates RNA-RNA or RNA-protein interactions to facilitate downstream activities, such as ribosomal RNA metabolism or pre-mRNA splicing.

 

Pseudouridylation is performed by a group of enzymes called pseudouridine synthases (PUS). These enzymes share a highly conserved core structure and a conserved catalytic aspartic acid for the reaction. Interestingly, each enzyme has its own set of RNA targets. To date, several clinical mutations are found in many PUS related to neuron development disorders.

 

Recently, we reported the biochemical analyses of human PUS3 and explained the mutations render protein stability, hence loss of function in patients-derived fibroblasts.

For more information, please go to the publication (https://pubmed.ncbi.nlm.nih.gov/36125428/).

Publications

1.     Biela A, Hammermeister A, Kaczmarczyk I, Walczak M, Koziej L, Lin TY* and Glatt S*. Structural insights into diverse modes of tRNA recognition. JBC. 299, 104966, 2023 (*Co-corresponding author)

2.     Jaciuk M, Scherf D, Kaszuba K, Gaik M, Koscielniak A, Krutyhołowa R, Rawski M, Indyka P, Biela A, Dobosz D, Lin TY, Abbassi NEH, Hammermeister A, Kosinski J, Schaffrath R and Glatt S. Cryo-EM structure of the fully assembled eukaryotic Elongator complex. NAR. 51, 2023

3.     Lin TY*, Smigiel R*, Kuzniewska B, Chmielewska J, Kosińska J, Biela M, Biela A, Kościelniak A, Dobosz D, Laczmanska I, Chramiec-Głąbik A, Jeżowski J, Nowak J, Gos M, Rzonca-Niewczas S, Dziembowska M, Ploski R and Glatt S. Destabilization of mutated human PUS3 protein causes intellectual disability. Human Mutation. 43, 2022. (*Co-first author)

4.     Lin TY* and Glatt S*. ACEing premature codon termination using anticodon-engineered sup-tRNA-based therapy. Molecular Therapy in Nucleic acids, 29, 2022 (*Co-corresponding author)

5.     Chramiec-Głąbik A, Rawski M, Glatt S and Lin TY*. Electrophoretic mobility shift assay (EMSA) and microscale thermophoresis (MST) methods to measure interactions between tRNAs and their modifying enzymes. Method in Molecular Biology (Springer). 2666:29-53, 2023 (*Co-corresponding author)

6.     Pakosz Z*, Lin TY*, Michalczyk E, Nagano S, Heddle J. Inhibitory Compounds Targeting Plasmodium falciparum Gyrase B. Antimicrobial Agents and Chemotherapy, 65, 2021 (*Co-first author)

7.     Lin TY*, Mehta R*, Glatt S. Pseudouridines in RNAs: switching atoms means shifting paradigms. FEBS Letters, 595, 2021 (*Co-first author)

8.     Abbassi NEH, Biela A, Glatt S*, Lin TY*. How Elongator Acetylates tRNA Bases. International Journal of Molecular Sciences, 21, 2020 (*Co-corresponding author)

9.     Chakraborti S, Lin TY, Glatt S, Heddle J. Enzyme encapsulation by protein cages. RSC Advances, 10, 2020

10.  Lin TY, Abbassi NEH, Zakrzewski K, Chramiec-Głąbik A, Jemioła-Rzemińska M, Różycki J & Glatt S. The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase. Nature Communications,10, 2019

11.  Dauden MI, Jaciuk M, Weis F, Lin TY, Kleindienst C, Abbassi NEH, Khatter H, Krutyhołowa R, Breunig KD, Kosinski J, Müller CW, Glatt S. Molecular basis of tRNA recognition by the Elongator complex. Science Advances, 5, 2019

12.  Lin TY and Glatt S. tRNA modification by Elongator protein 3 (Elp3). Encyclopedia of Inorganic and Bioinorganic Chemistry 2018

13.  Lin TY, Masunaga H, Sato R, Malay AD, Toyooka K, Hikima T, Numata K. Liquid crystalline granules align in a hierarchical structure to produce spider dragline microfibrils. Biomacromolecules, 4, 2017

14.  Glatt S, Zabel R, Kolaj-Robin O, Onuma OF, Baudin F, Graziadei A, Taverniti V, Lin TY, Baymann F, SeraphinB, Breunig K, Muller CW. Structural basis for tRNA modification by Elp3 from Dehalococcoides mccartyi. Nature Structure & Molecular Biology 23; 794-802, 2016

15.  Godonoga M, Lin TY, Oshima A, Sumitomo K, Cheung YW, Kinghorn AB, Dirkzwager RM, Kuzuya A, Tanner JA and Heddle JG. Specific recognition of a malaria protein biomarker by a DNA aptamer-origami nanoarray. SciRep. 6; 21266, 2016

16.  Nagano S, Lin TY and Heddle JG. Investigating the roles of the C-terminal domain of Plasmodium falciparum GyrA. PLoS ONE 10(11): e0142313, 2015

17.  Lin TY, Nagano S, and Heddle JG. Functional analyses of Toxoplasma gondii Gyrase Complex with dual features of gyrase and decatenase. Sci Rep. 5; 14491, 2015

18.  Chen BY, Chen XJ, Wu XW, Wang XL, Wang YJ, Lin TY, Kurata J, Wu J, Vonderfecht S, Huang H, Yee JK, Hu JD, and Lin RJ. TALEN-mediated gene disruption of microRNA-21 diminishes cell transformation and alters expression of cell- environment interaction genes. Cancer Letters. 356, 506-16, 2015.

19.  Nagano S, Lin TY, Edula R and Heddle JG. Unique Features of Apicoplast DNA Gyrases from Toxoplasma gondii and Plasmodium falciparum. BMC bioinformatics, 15, 416, 2014.

20.  Zang SB, Lin TY, Chen XJ, Gencheva M, Newo ANS, Yang LX, Rossi D, Hu JD, Lin SB, Huang AM, and Lin RJ. GPKOW is essential for pre-mRNA splicing in vitro and suppresses splicing defect caused by dominantnegative DHX16 mutation in vivo. Bioscience Reports, 34, 841-50, 2014.

21.  Huang CP, Tsai MF, Chang TH, Tang WC, Chen SY, Lai HH, Lin TY, Yang CH James, Yang PC, Shih JY*, Lin SB*. ALDH-Positive Lung Cancer Stem Cells Confer Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. Cancer Lett. 328, 144-51, 2013.

22.  Lin TY, Huang CP, Au LC, Chang YW, Hu CY, Lin SB. A cysteine-reactive alkyl hydroquinone modifies topoisomerase IIa enhances DNA breakage, and induces apoptosis in cancer cells. Chem. Res. Toxicol. 25, 2340-51, 2012.

23.  Gencheva M, Lin TY, Wu X, Yang L, Richard C, Jones M, Lin SB, Lin RJ. Nuclear retention of unspliced premRNAs by mutant DHX16/hPRP2, a spliceosomal DEAH-box protein. J Biol. Chem. 285, 35624-32, 2010.

24.  YR Chen, RYY Chiou, TY Lin, CP Huang, WC Tang, ST Chen, SB Lin. Identification of an alkylhydroquinone from rhus succedanea as an inhibitor of tyrosinase and melanogenesis. Journal of agricultural and food chemistry 57, 2200-2205, 2009

25.  Huang CP, Fang WH, Lin LI, Chiou RY, Kan LS, Chi NH, Chen YR, Lin TY, Lin SB. Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning. Toxicology and applied pharmacology 227 (3), 331-338, 2008

Publications

Chapter in book

Journal Article