HCI 2024 Prelim H2 Bio P3 Qn

© Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 HWA CHONG INSTITUTION JC2 Preliminary Examinations Higher 2 CANDIDATE NAME CT GROUP 23S7 __ CENTRE NUMBER INDEX NUMBER BIOLOGY Paper 3 Long Structured and Free-response Questions Candidates answer on the Question Paper. No Additional Materials are required. 9744/03 10 September 2024 2 hours INSTRUCTIONS TO CANDIDATES There are four question booklets (I - IV) to this paper. Write your name, CT group, Centre number and index number in the spaces provided at the top of this cover page and on the lines provided at the top of the cover pages of Booklets II, III and IV. Write in dark blue or black pen. You may use an HB pencil for any diagrams or graphs Section A Answer all questions in the spaces provided on the Question Paper. Section B Answer any one question in the spaces provided on the Question Paper. INFORMATION FOR CANDIDATES The use of an approved scientific calculator is expected, where appropriate. You may lose marks if you do not show your working or if you do not use appropriate units. The number of marks is given in brackets [ ] at the end of each question or part question. You are reminded of the need for good English and clear presentation in your answer. This document consists of 20 printed pages. For Examiners' Use Section A 1 / 30 2 / 10 3 / 10 Section B 4 or 5 / 25 Final Mark

2 © Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 SECTION A Answer all the questions in this section. QUESTION 1 Multistep signalling pathways control cellular functions through complex protein interactions. When some these pathways are dysregulated, it can lead to uncontrolled cell growth and cancer. (a) Outline the advantages of having such multistep pathways. [2] Chronic inflammation is known to contribute to cancer development. Researchers are examining how signalling molecules like interleukin-6 (IL6), a cytokine, is important for the body's response to infection and inflammation. Fig. 1.1 shows the IL6 signalling pathway. IL6 binds to its receptor, IL6R. The complex binds with gp130, which functions similarly to a receptor tyrosine kinase (RTK). The tyrosine kinase on gp130, JAK, activates downstream pathways that drive inflammation. gp130 IL6 IL6R STAT3 target genes that induce inflammation Fig. 1.1

3 © Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 (b)(i) Explain why IL6 cannot act directly on the DNA in the nucleus. [2] (b)(ii) Based on your knowledge on RTKs and with reference to Fig. 1.1, explain how IL6 leads to a cellular response. [5] (b)(iii) STAT3 activation is regulated by negative feedback. When STAT3 activation is excessive, more SOCS3 protein is synthesised, leading to ubiquitination of gp130. Suggest how regulation of STAT3 activation is an example of negative feedback. [3]

4 © Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 To understand the role of gp130 and IL6R on the IL6 signalling pathway, further studies were conducted on cell lines in vitro. The extracellular domain of gp130 is predicted to have six individual regions (R1-R6) as shown in Fig. 1.2. To investigate the region(s) required for activation of the IL6 signalling pathway, researchers created 3 deletion mutants. The sites of deletions of individual regions in the mutants Δ4, Δ5, Δ6 are marked by arrowheads. For example, Δ4 mutant has a missing R4 region. Fig. 1.2 Table 1.1 shows detection of STAT3 activation in gp130-expressing cells (wild type) and Δ4, Δ5, Δ6 mutants in the presence of IL6 and IL6R. Table 1.1 ( (c)(i) With reference to Fig. 1.2 and Table 1.1, identify and explain which region(s) of gp130 are required for IL6 signalling pathway. [3] wild type mutants Δ4 Δ5 Δ6 detection of STAT3 activation yes no no no extracellular domain R1 R2 R3 transmembrane domain R5 R6 R4 cytoplasmic domain gp130 Δ4 Δ5 Δ6

5 © Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 (c)(ii) Explain how the structure of the transmembrane domain of gp130 contributes to its function. [2] Different forms of IL6R also allow variation in IL6 signalling pathway. Fig. 1.3 shows how process Q at the RNA level can lead to two forms of IL6R, membrane-bound (M) and soluble form (S). Both forms can bind to the ligand IL6 and the receptor gp130. Fig. 1.3 (d) With reference to Fig. 1.3, explain the significance of process Q in the formation of membrane-bound and soluble forms of IL6R. [3] membrane-bound IL6R (M) soluble IL6R (S) Q 2 2 2 1 1 1 3 3 4 4 4

6 © Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 The IL6 signalling pathway is associated with prolonged chronic inflammation, which promotes cancer progression, such as pancreatic ductal adenocarcinoma (PDAC). PDAC starts in the pancreas, an organ that aids digestion and blood sugar regulation. Symptoms can include digestive issues, loss of appetite, fatigue, stomach pain and weight loss. By the time PDAC is diagnosed, it has often already spread, making early detection challenging. (e) Suggest why early detection of PDAC is challenging. [1] Several genes are implicated in the development of PDAC, including those in the IL6 signalling pathway, such as gp130, STAT3, and JAK. Table 1.2 gene mutations detected among PDAC patients / % gp130 60 STAT3 5 JAK 1 (f)(i) Table 1.2 shows mutations in genes of the IL6 pathway found in the pancreas of PDAC patients. Knowledge of these mutations is crucial for developing more effective treatments to treat PDAC by targeting the chronic inflammation due to excessive IL6 signalling. Using the information in Fig. 1.1 and Table 1.2, identify which gene is the best target for effective treatments and explain your choice. [3]

7 © Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 (f)(ii) Table 1.3 shows a few genes that are often found to be mutated in PDAC patients. With your knowledge and the relevant data provided, complete Table 1.3 to predict:  the level of gene expression, using “” or “”  if the gene is a proto-oncogene (POG) or tumour suppressor gene (TSG). Table 1.3 gene level of expression POG or TSG p53  TSG STAT3 SOCS3 [2] Question 1 continues on page 8

8 © Hwa Chong Institution 2024 9744 H2 Biology / JC2 Preliminary Examinations / Paper 3 (g) To investigate the effects of gp130 mutations on pancreatic cells, researchers used two groups of mice:  group A, a control group (gp130)  group B, with a specific gp130 deletion (gp130Δ). Both groups were treated with diethylnitrosamine (DEN), a chemical that damages the pancreas and can induce cancer, through injections at a dose of 25 mg/kg body weight. These injections started at 14 days old and were administered at various intervals until 40 weeks of age where the pancreas were harvested. Fig. 1.4 and 1.5 show:  cumulative tumour diameter measured at 24 weeks of age – this reflects tumour initiation  number of tumours counted at 40 weeks of age – this reflects tumour progression. Fig. 1.4 Fig. 1.5 (g)(i) Calculate the amount of DEN to be injected into a 14-day old mouse that weighs 10 g. You should show your working. amount of DEN injected = µg [1] (g)(ii) Discuss the effect of gp130 on tumour initiation and tumour progression. [3] [Total: 30] gp130 gp130Δ gp130 gp130Δ cumulativ