Important discoveries

Question 1

Hill et al (2016)

Answer 1

Certain gut bacteria are necessary for the pancreas to populate itself with a robust number of beta cells during development by releasing a protein called BefA that causes the beta cells to multiply.

Question 2

Andersson et. al. (2012)

Answer 2

Screening small molecules that act on the adenosine signaling pathway found an adenosine agonist called NECA which is a potent enhancer of β cell regeneration in both zebrafish and mice.

Question 3

Cohen et al (2001)

Answer 3

Selective deletion of leptin receptor in specific neurons leads to obesity in mice showing that the brain is a direct target for the weight-reducing and neuroendocrine effects of leptin.

Question 4

Robins et al (2013)

Answer 4

α-tanycytes are self-renewing cells that form the critical component of a hypothalamic stem cell niche. Their proliferation is governed by local fibroblast growth factor signalling.

Question 5

Nasif et al (2015)

Answer 5

The early expression/coexpression of Islet 1 (ISL1) in the developing hypothalamus is essential for hypothalamic Pomc expression and therefore normal adiposity in mice and zebrafish throughout the entire lifetime.

Question 6

Scarlett et al (2016)

Answer 6

Administering rat and mice models of T2D with an intracerebroventricular injection of FGF1 initiates sustained diabetes remission, which does not cause weight loss or hypoglycemia.

Question 7

Nusslein-Volhard and Weischaus (1980)

Answer 7

Mutagenesis screen in Drosophila and discovered patterning genes including Wg.

Question 8

Clevers and Nusse (2014)

Answer 8

At the bottom of the intestinal crypt, paneth and stromal cells supply Wnt signalling to sustain the self-renewal of stem cells exclusively at the bottom. Cells moving upwards begin to differentiate.

Question 9

Myant et al (2013)

Answer 9

After APC is lost, RAC1 uses ROS production and NF-κB activation a critical to cause expansion of the LGR5 intestinal stem cell, progenitor hyperproliferation, and transformation to initiate colorectal cancer.

Question 10

Taipale et al (2000)

Answer 10

Many tumours are caused by mutations that activate the proto-oncogene Smoothened (SMO) or that inactivate the tumour suppressor Patched (PTCH), causing increase Hh signalling. Cyclopamine can block activation of the Hh response pathway and abnormal cell growth associated with both types of oncogenic mutation.

Question 11

Davies et al (2002)

Answer 11

The RAS–RAF–MEK–ERK–MAP kinase pathway mediates cellular responses to growth signals. BRAF somatic missense mutations in kinase domain present in 66% of malignant melanomas and at lower frequency in a wide range of human cancers causing increased kinase activity.

Question 12

Yang et al (2010)

Answer 12

PLX4702, a small-molecule inhibitor of BRAF(V600E) kinase activity potently inhibits proliferation and ERK kinase and ERK phosphorylation. In xenograft models of BRAF(V600E)-expressing melanoma, PLX4702 treatment caused partial or complete tumor regressions.

Question 13

White et al (2011)

Answer 13

Neural crest progenitors from zebrafish transgenic embryos mitfa:BRAF(V600E) lacking p53 fail to terminally differentiate. DHODH-class Leflunomide exerts inhibits the transcriptional elongation of genes that are required for neural crest development and melanoma growth. DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies.

Question 14

Ceol et al (2011)

Answer 14

Zebrafish melanoma model were used to test for genes on chromosome 1 that associate with BRAFV6003. They found SETDB1, an enzyme that methylates histone H3 on lysine 9 which accelerates melanoma formation by dysregulating HOX genes.

Question 15

Wichterle et al (2002)

Answer 15

Relevant signaling factors can induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo.

Question 16

Miles et al (2004)

Answer 16

MNs can be derived from transgenic mouse ES cell line where GFP is under control of Hb9 promoter. ES cells were exposed to RA and Shh to stimulate differentiation. Resultant motor neurons develop appropriate transmitter receptors, intrinsic properties for appropriate action potential firing and functional synapses with muscle fibers.

Question 17

Grand Challenges in Mental Health

Answer 17

Aim to bring mental, neurological and substance use disorders to the forefront of global attention and scientific inquiry, identifying research priorities that, if addressed within the next decade, could lead to substantial improvements in the lives of people living with neuropsychiatric illnesses.

Question 18

Eachus et al (2017)

Answer 18

Adult zebrafish homozygous mutant for disc1 show aberrant behavioural responses to stress. In disc1 mutant embryos neuronal differentiation is compromised in rx3-derived, ff1b+ and crh neurons. Altered crh levels fail to upregulate cortisol levels when under stress and do not modulate normal social behaviour.

Question 19

Hall, Rosbash and Young (Nobel Prize 2017)

Answer 19

Identified the protein components of the circadian clock machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell mostly determined by an inhibitory feedback loop of the PER protein.

Question 20

Landgraf et al (2016)

Answer 20

Disrupting suprachiasmatic nucleus circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression.

Question 21

Wulff et al (2012)

Answer 21

Significant sleep/circadian disruption occurred in schizophrenic participants. Half showed severe circadian misalignment in sleep-wake and melatonin cycles, and the other half showed patterns from excessive sleep to highly irregular and fragmented sleep epochs but with normally timed melatonin production.

Question 22

Clancy et al (2001)

Answer 22

Drosophila gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor signaling pathway. Mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes.

Question 23

Tsuda et al (2010)

Answer 23

Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila. IDE is implicated in the pathogenesis of type 2 diabetes mellitus and Alzheimer’s disease.

Question 24

Moore et al. (1998)

Answer 24

Using an inebriometer to measure ethanol-induced loss of control, cheapdate was identified, a mutant with enhanced sensitivity to ethanol which can be reversed by treatment with agents that increase cAMP levels or PKA activity. This shows that cAMP transduction pathway is involved.

Question 25

Kang et al (2009)

Answer 25

By hitting cancer cells with chemotherapy at a time when their ability to repair themselves is minimal i.e. at night, you should be able to maximize effectiveness and minimize side effects of treatment.

Question 26

Fatehullah et al (2016)

Answer 26

In vitro 3D organoid models facilitate an accurate study of a range of in vivo biological processes including tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage.