Gene expression is controlled by a number of features

Question 1

Stem cells what are they

Answer 1

Stem cells are unspecialised cells capable of:

Self renewal; can divide to replace themselves

Specialisation/differentiation; can develop into other types of cell

Question 2

Stem cell specialisation

Answer 2

A stimulus e.g. a chemical causes the the selective activation of genes; some cells are activated whilst others are deactivated

mRNA is only transcribed from specific, active genes and translated onto ribosomes/proteins

These proteins modify the cell permanently and determine the cell structure and control cell processes

Question 3

Totipotent cells

Answer 3

Occur for a limited time in early mammalian embryos

Can divide and differentiate into every cell type in body (including the cells that support the embryo, such as the placenta)

Question 4

Pluripotent cells

Answer 4

Found in embryos

Can divide and differentiate into most cell types (every cell type in body but not the cells of the placenta)

Question 5

Multipotent cells

Answer 5

Found in mature animals

Can divide and differentiate into a limited number of cell types

e.g. multipotent cells in bone marrow can differentiate into different types of blood cell

Question 6

Unipotent cells

Answer 6

Found in mature mammals

Can divide and differentiate into just one cell type

e.g. cardiomyocytes (cardiac muscle cells) can be made from a type of unipotent stem cells and epidermal skin cells can only be made from another type of unipotent stem cell

Question 7

Stem cells implementation in medicine

Answer 7

Regrow damaged tissues in accidents (i.e. skin grafts) or by disease (i.e. neuro-degenerative diseases, Parkinson’s disease)

Drug testing – used to grow artificial tissues

Developmental biology research – provide insight into embryological development

Question 8

Induced pluripotent stem cells (iPS cells) how are they produced and why are they useful

Answer 8

1. Produced from adult somatic cells i.e. non-pluripotent cells or fibroblasts
2. These adult pluripotent cells are created by putting specific protein transcription factors associated with pluripotency into cells, causing the cell to express genes associated with pluripotency (reprogrammed)
3. Cells are cultured which leads to the production of induced pluripotent stem cells

This is used in medical treatment instead of embryonic cells which is useful because:

No immune rejection as can be made using patient’s own cells

Overcome some ethical issues with using embryonic stem cells e.g. no destruction of embryo and adult can give permission

Question 9

Evaluate use of stem cells in treating human disorders

Answer 9

For:

The use of embryonic cells; tiny ball of cells, incapable of feeling pain, not equivalent to a human and they would otherwise be destroyed (if from infertility treatment which creates more than needed)

Duty to apply knowledge to relieve human suffering

Against:

The use of embryonic cells; embryo is a potential human; should be given rights

Still under research; Induced pluripotent stem cells – cannot yet reliably reprogramme stem cells, so it could begin to multiply out of control, and cause tumours

Question 10

Transcription factors

Answer 10

Transcription factors are protein molecules

They move from the cytoplasm to the nucleus

In the nucleus they bind to DNA at a specific DNA base sequence on a promoter region (near the start of their target genes)

Stimulate (activators) or inhibit (repressors) transcription (the production of mRNA of target genes by helping or preventing RNA polymerase from binding to the start of the target gene

Question 11

The role of oestrogen in initiating transcription (activator)

Answer 11

1. Oestrogen, a steroid hormone, can diffuse across the phospholipid bilayer of the cell-surface membrane as it’s lipid soluble.
2. In cytoplasm, oestrogen binds to a receptor of an inactive transcription factor, forming a hormone-receptor complex
3. Inactive transcription factor changes shape, resulting in active transcription factor
4. Diffuses from cytoplasm into
   nucleus and binds to specific DNA
   base sequence on a promotor
   region
5. Stimulates transcription of genes
   by helping RNA polymerase to bind

Question 12

Epigenetics what is it

Answer 12

Changes in gene function (expression) without changes to the base sequence of DNA, caused by changes in the environment

Epigenetics can determine whether or not a gene is expressed

Organisms inherit epigenetic changes from their parents i.e. offspring can be affected by environmental changes that affected their parents or grandparents

Question 13

How epigenetics can inhibit transcription

Answer 13

Via methylation of DNA:

Methyl groups are added to cytosine bases in DNA and changes the DNA structure; nucleosomes pack more tightly together

Prevents transcription factors from binding so that RNA polymerase cannot bind (genes not transcribed).

This is irreversible

Via decreased acetylation of associated histones:

Decreased acetylation of histones increases positive charge of histones.

Histones bind to DNA (which is negatively charged) more tightly

Prevents transcription factors from binding; genes not transcribed

Reversible

The nucleosome is the DNA wrapped around histone proteins; how closely the DNA and histone are packed together affects transcription

Question 14

Relevance of epigenetics on disease development and treatment, especially cancer

Answer 14

Epigenetic changes that increase the expression of an oncogene, or that silence a tumour suppressor gene, can lead to tumour development

Tests can be used to see if a patient has abnormal levels of methyl and acetyl – early indicator of cancer (called a biomarker)

Could be manipulated to treat cancer i.e. drugs to prevent histone acetylation/DNA methylation that may have caused these genes to be switched on/off, resulting in cancer

Question 15

RNA interference (RNAi)

Answer 15

RNA molecules inhibit translation of mRNA produced by transcription (gene is ‘switched on’ but encoded protein not produced i.e a ‘silenced’ gene)

Small, double-stranded RNA molecules stop mRNA from target genes being translated into proteins

The molecules involved in RNAi are called siRNA (small interfering RNA) and miRNA (micro RNA)

Occurs in eukaryotes

miRNA expression deregulated in many human diseases including cancer, so it offers opportunities as biomarkers and novel therapies

Question 16

Small interfering RNA (siRNA)

Answer 16

Formed as double-stranded molecules 21-25 bp long, one strand incorporated
into a protein-based RISC (RNA-induced silencing complex)

Single-stranded siRNA within a RISC binds to a molecule of target mRNA containing a sequence of bases complementary to its own

Proteins associated with the siRNA cut the mRNA into fragments i.e. mRNA is hydrolysed

Similar process occurs with miRNA in plants

Question 17

Micro-RNA (miRNA)

Answer 17

Formed as hair-pin bends of RNA but processed into single-strands 22-26 nucleotides long, both become incorporated into a protein-based RISC (RNA-induced silencing complex)

Less specific than siRNA, so it may target more than one mRNA molecule

Single-stranded miRNA within a RISC (multiprotein complex) binds to a molecule of target mRNA containing a sequence of bases complementary to its own

miRNA-protein complex physically blocks the translation of the target mRNA i.e. translation is stopped

Question 18

Cancer and classification of tumours

Answer 18

Cancer is the uncontrolled cell division of cells which leads to a tumour that is malignant (spread easily throughout the body via metastasis)

Benign tumours are non-cancerous

Question 19

Features of a benign tumour

Answer 19

Grow slowly (rare mitoses)

Well differentiated/specialised (cells retain function and normal shape, regular nuclei)

Normal, regular nuclei

Well defined borders/boundary; cell adhesion molecules stick cells together and to a particular tissue, often surrounded by a capsule so remain within tissues

Easy to treat - can normally be removed by surgery, rarely returns

Question 20

Features of a malignant tumour

Answer 20

Grow rapidly (more frequent and/or
abnormal mitoses)

Cells become unspecialised/poorly differentiated

Irregular, larger/darker nuclei

Irregular/poorly defined borders and not encapsulated; cells break off (+ grows projections into surrounding tissues) so metastasis occurs

Removed by radiotherapy/chemotherapy as well as surgery; can be life threatening and recurrence more likely

Question 21

Tumour suppressor genes function and role in tumour growth

Answer 21

Their normal function is to code for proteins involved in control of cell division

In particular, stopping the cell cycle when DNA damage is detected

Also involved in causing self-destruction of the cell (apoptosis) where damaged DNA cannot be repaired

In the development of tumours, the mutation of tumour suppressor genes alters amino acid sequence and tertiary structure of protein which leads to a non-functional protein

Increased methylation could also cause this as it prevents transcription/expression of protein

Damaged DNA not repaired/cells not killed, leading to uncontrolled cell division

Question 22

Proto-oncogenes function and role in tumour growth

Answer 22

Their normal function is to code for proteins involved in control of cell division

In particular, stimulating cell division (when growth factors attach to receptors on cell membrane, so cell division is required)

In the development of tumours, mutation could turn it into permanently activated oncogene

Decreased methylation/increased acetylation causes excess transcription

Leading to cell division being permanently activated and thereby rapid, uncontrolled cell division occurs

Question 23

The role of increased oestrogen concentrations in the development of some breast cancers

Answer 23

Areas of high oestrogen concentration such as adipose tissues in breasts are where cell division is more likely to become uncontrolled

Oestrogens ability to stimulate cell division can assist cancerous cells if they occur, helping tumours form quickly

Growth of cancer minimised with drugs blocking production/action of oestrogens in the breasts

e.g. Tamoxifen prevents oestrogen binding to receptor