Nov 13 - 19, 2020
RPG Seminar Series (2020-11-13 & 2020-11-19)
Date: Friday, 13 November 2020
Venue: Seminar Room 1 & 2, G/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road
Time: 5:00 p.m. - 6:00 p.m.
Time: 5:00 p.m.
Speaker: Miss Raissa Regina NG (PhD candidate)
Primary Supervisor: Prof. Michael Shing Yan HUEN
Presentation Title: Role of ARIP4 in DNA damage driven transcription
Emerging evidence indicates that TOP2β-induced DNA double strand breaks (DSBs) at gene promoters underlie optimal induction of gene expression. However, mechanistically how DSB processing factors participate in transcriptional control remains obscure.
Androgen Receptor Interacting Protein 4 (ARIP4) was first identified as a coregulator of Androgen Receptor-mediated transcription and is speculated to function as a repair factor due to its structural similarity to other damage factors. Indeed, here we show that ARIP4 is recruited to sites of DNA damage in a PARP1 and transcription-dependent manner. Depletion of ARIP4 results in persistent DNA damage signaling and unresolved DSBs. By using a reporter cell that allows monitoring of the effects of local DSBs on transcription in situ of the gene, ARIP4 accumulates at sites of active transcription even without induction of exogenous DSBs. Astoundingly, depletion of ARIP4 leads to defective transcriptional activation. As the reporter appears to faithfully mimic the physiological conditions of TOP2-dependent transcriptional induction, this serves as preliminary data that implicates ARIP4 in DSB-driven transcription, which may have clinical implications in cancers that depend on transcription for growth, radioresistance and metastatic potential.
Time: 5:30 p.m.
Speaker: Mr. Kah Chee POW (PhD candidate)
Primary Supervisor: Prof. Quan HAO
Presentation Title: Co-crystallization of Stilbene O-methyltransferases (SOMTs) with resveratrol
Stilbene O-methyltransferase (SOMT) catalyzes the methylation of resveratrol to synthesize pterostilbene. Pterostilbene offers greater bioavailability while both compounds have been actively exploited for health benefits in human. Our interest is to resolve the structure of SOMT and elucidate the mechanism of resveratrol methylation at structural basis. In this study, X-ray crystallography approach is employed to resolve the structure of two SOMT homologs (SOMT1 & SOMT2). The isothermal titration calorimetry (ITC) study had revealed that their binding affinity contrasted by hundreds-fold, where OMT2 binds resveratrol at sub-micromolar level (dissociation constant, Kd ≈ 500 nM). Here, we report the success in crystallizing OMT1 and OMT2 in the presence of resveratrol. In which, OMT2 crystals were further exploited by soaking with SAM substrate (which activate the methylation) to capture the dynamic of the catalytic reaction. Next, X-ray crystallography will be employed to resolve and address the difference in binding affinity at structural basis.
Date: Thursday, 19 November 2020
Venue: Cheung Kung Hai Lecture Theatre 2, G/F, William M.W. Mong Block, Faculty of Medicine Building, 21 Sassoon Road
Time: 5:00 p.m. - 6:00 p.m.
Time: 5:00 p.m.
Speaker: Miss Ran CHEN (PhD candidate)
Primary Supervisor: Prof. Dong-Yan JIN
Presentation Title: HBX regulates the gene transcription levels by recruiting HUSH complex
It is reported that HUSH complex inhibits the integration and transcription process of retrovirus, including HIV-2, MMLV and so on. Both the DNA templates of HBV and retrovirus result from reverse transcription process. Therefore, we wonder if HUSH complex can have any effects on HBV transcription process, vice versa. Surprisingly, as the only transcriptional factor of HBV, HBX does not degrade HUSH complex at RNA and protein levels. Actually, HBX can bind and stabilize HUSH complex at protein levels. After searching the literature, we found that CDH1 gene encoding E-cadherin can be repressed by both of Mpp8 and HBX at the transcriptional level. We found HBX loses the repressed ability of CDH1 after knocking down any component of HUSH complex. Based on these findings, we would like to come up our hypothesis that HBX regulates the gene transcription levels by recruiting HUSH complex. In addition, positive or negative regulation depends on the specific pattern circumstance of target sequence.
Time: 5:30 p.m.
Speaker: Miss Wai Yin CHENG (PhD candidate)
Primary Supervisor: Dr. Raymond Chuen Chung CHANG
Presentation Title: Investigating the significant roles of PKR on systemic inflammation triggered neuroinflammation and cognitive dysfunctions
Increasing lines of evidence have shown that systemic inflammation may contribute to neuroinflammation and accelerate the progression of neurodegenerative diseases. Double-stranded RNA-dependent protein kinase (PKR) is one of the major signaling molecules to regulate immune responses by regulating activation of macrophages, different inflammatory pathways and formation of inflammasome. Meanwhile, PKR in neurons mediates stress responses of amyloid-β to trigger apoptosis and affect different domains of cognitive functions. In this study, we aim at investigating whether PKR can be a pharmacological target for preventing both systemic inflammation-triggered neuroinflammation and systemic inflammation-induced cognitive dysfunctions. A non-bacterial endotoxin mouse model of laparotomy is adopted to address the systemic inflammation triggered by surgery. Our preliminary findings reveal that laparotomy induced peripheral inflammation and neuroinflammation in C57BL/6J wild type mice; while genetic knockout of PKR in mice could attenuate both systemic and neural inflammation.
ALL ARE WELCOME
Should you have any enquiries, please feel free to contact Miss Cecilia Chan at 3917 9493.